Molecule of pharmaceutical interest comprising at its n-terminal a glutamic acid or a glutamine in the form of a physiologically acceptable strong acid

ABSTRACT

The invention concerns a molecule of pharmaceutical interest, preferably a major histocompatibility complex (MHC) ligand, comprising a glutamic acid or a glutamine at its N-terminal, in the form of a physiologically acceptable addition salt, and a vaccine comprising such a ligand.

[0001] The subject of the present invention is a molecule ofpharmaceutical interest, preferably a ligand for the MajorHistocompatibility Complex (MHC), containing a glutamic acid or aglutamine at its N-terminal end, which exists in the form of aphysiologically acceptable addition salt with a strong acid, and avaccine comprising such a ligand.

[0002] Vaccination is an effective means for preventing or reducingviral or bacterial infections. The vaccine antigens when administeredalone to the host are often not sufficiently immunogenic to induce animmune response, and should therefore be combined with an adjuvant orcoupled to a carrier protein in order to elicit (or increase) theirimmunogenicity. Under these conditions, only a humoral type immuneresponse may be induced. However, in the context of an antiviraltherapy, the generation of cytotoxic T lymphocytes (CTL) capable ofrecognizing and destroying the virus is of primary importance (Bachmannet al., Eur. J. Immunol., 1994, 24, 2228-2236; Borrow P., J. Virol.Hepat., 1997, 4, 16-24), as demonstrated by numerous studies showing invivo the protective role of the responses directed against the viralepitopes (Arvin A. M., J. Inf. Dis., 1992, 166, pp. 35-41; Koszinowskiet al., Immunol. Lett., 1987, 16, 185-192).

[0003] The importance of the CTL and helper T responses has also beenindeed described for vaccines against parasites such as Plasmodiumfalciparum, the agent responsible for Malaria (Le et al., Vaccine, 1998,16, 305-312).

[0004] The vital role of the CTL responses has also been greatlydocumented in antitumor responses, in particular those directed againstmelanoma cells (review in Rivoltini et al., Crit. Rev. Immunol., 1998,18, 55-63). The CTL epitope(s) (peptide sequences interacting with theclass I molecules and presented to the CD8+ T lymphocytes) have beendefined for several antigens. However, the difficulty lies in thegeneration of CTL in vivo, due to the low immunogenicity of thesepeptides (Melief, Adv. Cancer Res., 1992, 58, 143-175; Nandaz andSercaz, Cell, 1995, 82, 13-17).

[0005] Numerous ligands for the MHC (class I and II) and in particularfor the CTL epitope peptides have been identified (HG Rammensee et al.,Immunogenetics, 1999, 50, 213) and some of their sequences areaccessible on the Internet in public databases. There may be mentionedin particular the bases SYFPEITHI (http://www.uni-tuebingen.de/uni/kxi/)and MHCPEP (http://wehih.wehi.edu.au/mhcpep/). Likewise, supertypes ofthe principal HLAs have been described (Sette et al., Immunogenetics,1999, 50, 201-212).

[0006] The importance of these MHC ligands is confirmed by theincreasing number of clinical studies in humans of these compounds ascandidate vaccines against various pathologies and in particular asanti-melanoma vaccines (epitopes m27-25 MART 1, g209-217, g280-288,gp100, MAGE 3), as anti-HIV vaccine (Klinguer et al., Vaccine, 2000, 18,259-267) or as anti-HBV vaccines of the anti-HBV lipopeptide type(Livingston et al., J. Immunol., 1999, 162, 3088-3095).

[0007] However, the difficulty of these studies lies in the fact thatthe peptides used are difficult to preserve before their administrationto the patients, which can lead to a reduction in their vaccine power,and to a more rapid degradation in vivo.

[0008] To stabilize a peptide intended for pharmaceutical use which hasa glutamic acid or a glutamine at the N-terminus in the form of a saltcompatible with administration to humans, the strategy normally used bypersons skilled in the art is to synthesize the pyroglutamic derivativeof this peptide, as the two examples below of Buserelin and Gonadorelin(LH-RH analogs, European Pharmacopoeia, 1999) illustrate:

[0009] This moreover makes it possible to increase the half-life of thepeptide by limiting its proteolytic degradation by N-aminopeptidases.

[0010] However, when this method is used to stabilize an MHC ligand suchas the ELA decapeptide (CTL epitope of sequence ELAGIGILTV and offormula C₄₅H₈₀N₁₀O₁₄₌985 Da), the PyrELA derivative obtained (ofsequence PyrELAGIGILTV and of formula C₄₅H₇₈N₁₀O₁₃₌967 Da) no longerexhibits the desired vaccine activity and is in particular practicallyinactive from the point of view of a CTL response. This structuralmodification is nevertheless minor: it involves the cyclization of theN-terminal α-amino functional group of the glutamic acid with its ownγ-carboxylic functional group and loss of a molecule of water. Indeed,the peptides having an amino acid of the glutamic acid (Glu, E) orglutamine (Gln, Q) type at their N-terminal end cyclize with the freeγ-carboxylic acid functional group to form a pyroglutamate according tothe reaction defined below:

[0011] The absence of a vaccine activity for these peptides is all themore surprising since the reduction in mass between the ELA decapeptideand the PyrELA derivative obtained is only 18 Daltons, while theremainder of the structure remains unchanged:

[0012] It has also been observed that the synthesis of anotherderivative of the ELA peptide acetylated on the amine functional groupof the glutamic acid so as to prevent cyclization to pyroglutamate(AcELA peptide, of sequence AcELAGIGILTV and of formulaC₄₇H₈₂N₁₀O₁₅₌1027 Da, see above) makes it possible to solve the problemof stability but causes the AcELA derivative thus obtained to lose theentire vaccine activity, and in particular the CTL cell generatingactivities.

[0013] This acetylation reaction is nevertheless a minor modification ofthe structure of the peptide conventionally used by persons skilled inthe art to improve the stability of a peptide (Brinckerhoff et al., Int. J. Cancer, 1999, 83, 326): it involves the replacement of one of theprotons of the N-terminal NH₂ functional group by an acetyl group CH₃COwith a small increase in mass (42 Da over 985 Da), the remainder of thestructure remaining unchanged.

[0014] Likewise, Elliott et al. (Vaccine, 1999, 17, 2009-2019) havedescribed problems of stability of CTL epitopes containing methionines(oxidation to a sulfoxide) or glutamic acids at the N-terminal position(peptide EEGAIVGEI, derived from the influenza protein NSP-1 of theinfluenza virus (amino acids 152-160) and corresponding to a restrictedH-2Kk mouse CTL epitope). It was observed that this peptide cyclizesspontaneously to pyroglutamate (30% in 2 months) when it is formulatedwith an adjuvant solution of the Montanide ISA 720 type. The authorsraise the problem that this degradation poses with respect to thedesired vaccine activity, without providing a solution thereto.

[0015] In addition, practically all the peptides obtained by chemicalsynthesis are purified by reversed-phase HPLC with the aid of eluentscontaining trifluoroacetic acid (TFA) before being freeze-dried. Thepurified peptides obtained are positively charged and exist in the formof a trifluoroacetate salt (RNH₃ ⁺,CF₃CO₂ ⁻). The quantity oftrifluoroacetate and of residual trifluoroacetic acid is in generalproportional to the number of basic amino acids (Lysine, Arginine andHistidine) contained in the sequence as well as the amine functionalgroup of the N-terminal amino acid. Peptides in trifluoroacetate formare commonly used for preclinical experiments in vitro and in vivo inanimals. For a pharmaceutical use in humans, this salt form is howevernot accepted in particular during the final stages of purificationsbecause trifluoroacetic acid is part of a class of solvents (class IV)whose toxicology is not perfectly documented (Leblanc et al., STPPharma, 1999, 9, 334-341). Thus, none of the peptides which haveobtained a marketing authorization (Somatostatin, Tetracoside,Desmopressin, Calcitonin, Buserelin, Gonadorelin, and the like) were inthe trifluoroacetate form, as may be observed in the EuropeanPharmacopoeia monographs (Ph. Eur. 1999), but rather in the acetateform. The quantity of residual trifluoroacetic acid tolerated in thesepeptides is in fact extremely limited.

[0016] Moreover, a recent study (Cornish et al., Am. J. Physiol.Endocrinol. Metab., 1999, 277, E779-E783) has shown that severalsynthetic peptides (Amylin, Calcitonin) in trifluoroacetate form aretoxic for cells in culture (osteoblasts and chondrocytes).

[0017] A solution for solving these various problems of toxicity oftrifluoroacetic acid has been proposed by Marchand et al. (Int. J.Cancer, 1999, 80, 219-230), who report results of a clinical studydemonstrating a tumor regression in patients suffering from a melanoma.The active ingredient used is the nonapeptide MAGE-3 having the sequenceEVDPIGHLY (SEQ ID No. 273), which possesses a glutamic acid at theN-terminal. The peptide was used in patients in the acetate form whichis the form used in practically all the peptides administered to humans.

[0018] However, acetic acid is a weak acid, which confers increasedinstability on the peptide. This forces investigators to store thepeptide at −80° C. (liquid nitrogen) in freeze-dried form and toresolubilize it immediately before the injection, which involves ahighly constraining cold chain.

[0019] The present invention proposes to solve these problems ofstructural instability, of preservation over time, of toxicity and ofbiological activity.

[0020] Indeed, it has been observed, surprisingly, that the molecules ofpharmaceutical interest, in particular the MHC ligands, possessing aglutamic acid or a glutamine at their N-terminal end can be stabilizedin the form of an addition salt with a strong acid, and that this makesit possible both to maintain the biological activity and to obtain easypreservation of the peptide or analog in a stable form, which allows itstherapeutic use in humans.

[0021] The expression “molecule of pharmaceutical interest” isunderstood to mean in particular the MHC ligands, the natural orsynthetic molecules having an epitope for the generation of antibodies,the molecules derived from receptor ligands, and exhibiting an agonistor antagonist activity with respect to these receptors, or possessing anantibiotic, antifungal or antiviral activity. The molecules oftherapeutic interest according to the invention are all characterized inthat they possess a glutamic acid or a glutamine at their N-terminalend. The preferred molecules of pharmaceutical interest according to thepresent invention are the MHC ligands.

[0022] The subject of the present invention is thus in particular an MHCligand containing at its N-terminal end a glutamic acid or a glutamine,characterized in that it exists in the form of a physiologicallyacceptable addition salt with a strong acid.

[0023] The physiologically acceptable addition salt with a strong acidmay be chosen in particular from the addition salts with stronginorganic or organic acids.

[0024] It is preferably chosen from the methanesulfonate (or mesilate),hydrochloride, hydrobromide, sulfate, nitrate and phosphate and morepreferably from the hydrochloride, sulfate, nitrate andmethanesulfonate.

[0025] These addition salts with a strong acid are physiologicallyacceptable for a therapeutic use in humans. For example, Protamine(obtained by extraction from sperm or from soft roe of fish and whichrequires a strong acid salt in order to be solubilized) is registered inthe hydrochloride form, on the one hand, and in the sulfate form, on theother (Ph. Eur., 1999).

[0026] The MHC ligands for the purposes of the present invention are inparticular the MHC class I and II ligands. MHC is an important group ofproteins involved in the presentation of antigens to the T lymphocytes.The MHC class I molecules are integral membrane proteins which are foundon all nucleated cells and the platelets. The MHC class II molecules areexpressed on the B cells, the macrophages, the monocytes, theantigen-presenting cells and certain T cells. The B cells arelymphocytes which, in a mature form, present at their surfaceimmunoglobulins acting as “receptor for the antigen”. The T cells arelymphocytes which express their receptor for the antigen (TcR) and aredifferentiated into 2 subpopulations: T helper cells (Th or T helper)and cytotoxic T cells (CTL). The Th cells help the B cells to divide, todifferentiate and to produce antibodies. The majority of the Th cellsare CD4+ (specific surface marker) and recognize the antigen presentedat the surface of the antigen-presenting cells, in combination with theMHC class II molecules. The cytotoxic T cells are capable of destroyingthe target cells infected by viruses or allogenic cells. The majorityare CD8+ and recognize the antigen associated with the MHC class Imolecules at the surface of the target cell. The recognition of theantigen occurs by formation of a complex comprising in particular theMHC molecule presenting an MHC ligand, and the T cell receptor (TCR).

[0027] The molecules of pharmaceutical interest, in particular the MHCligands according to the present invention, may be chosen from naturalor synthetic molecules, and, inter alia, from proteins, peptides,multi-epitope polypeptide constructs, or peptide analogs of thepseudopeptide, retro-inverso or peptoid type, peptido-mimetics, andlipopeptides. These molecules may also partly consist of a peptidechain, with the replacement of certain amino acids by amino acidanalogs, or a chain having branches. These molecules may also exhibitvarious modifications which are observed on the natural proteins orpeptides (for example O- or N-glycosylation).

[0028] In a preferred embodiment of the invention, the MHC ligandsaccording to the present invention are chosen from the CTL epitopes,that is to say those which allow the generation of cytotoxic Tlymphocytes, and in particular from those which exist in the form of anoctapeptide, a nonapeptide or a decapeptide.

[0029] The MHC ligand may also be chosen from the ligands described inthe databases SYFPEITHI or MHCPEP, cited above, and which contain, attheir N-terminal end, a glutamic acid or a glutamine.

[0030] This ligand may be chosen in particular from the MHC ligands(ligands for the MHC class I or II molecules) included in the groupconsisting of the peptides corresponding to the sequences SEQ ID No. 1to SEQ ID No. 694.

[0031] In an embodiment of the invention which is even more particularlypreferred, it is chosen from the following peptides: SEQ ID NamesSequences HLA No. ELA MART-1 26-35 A27L ELAGIGILTV A2 81 ELA MART-126-35 EAAGTGILTV A2 112 MAGE-1 161-169 EADPTGHSY A1 2 MAGE-3 168-176EVDPIGHLY A1 273 HER-2/neu 950-958 ELVSEFSPRM A2 110 HCV-1 env E 66-75QLRRHTDLLV A2 464 NY-ESO-1 155-163 QLSLLMWIT A2 466 HIV nef 73-82QVPLRPMTYK A3 567 Influenza NP 380-388 ELRSRYWAI B8 166 HIV gag p24262-270 EIYKRWIIL B8 10 HIV gag p17  93-101 EIKDTKEAL B8 692 InfluenzaNP 339-347 EDLRVLSFI B*3701 257 EBNA 6 130-139 EENLLDFVRF B*4403 568

[0032] The ligands according to the invention may also be chosen fromthe multi-epitope polypeptide constructs having an amino acid of theglutamic acid (Glu, E) or glutamine (Gln, Q) type at the N-terminal endsuch as the following peptide (SEQ ID No. 695):

[0033] NEF 117 EWRFDSRLAFHHVAREHPEYFNKNK(Palm)NH₂ (anti-HIV lipopeptidein clinical phase I: Klinguer, et al., Vaccine, 1999, 18, 259-267).

[0034] The peptide analogs may be chosen from those described inapplication FR276307 which contain, at their N-terminal end, a glutamicacid or a glutamine.

[0035] More preferably, the invention relates to the MHC ligand havingthe sequence ELAGIGILTV, in sulfate form or, even more preferably, inhydrochloride form.

[0036] The invention also relates to a pharmaceutical compositioncomprising at least one molecule of pharmaceutical interest according tothe invention.

[0037] This pharmaceutical composition may in particular be intended forthe treatment of various immunopathologies: immunodeficiency, autoimmunediseases, hypersensitivities, allergies or for avoiding graftrejections. Depending on the molecule used, a composition according tothe invention may also be used for an antibiotic, antiviral orantifungal purpose, or may be intended for the treatment of diseaseslinked to hormonal disruptions, or to diseases of the central nervoussystem.

[0038] The compositions according to the invention may also be used inthe veterinary field. Indeed, the same problems of structuralinstability, of preservation over time, of toxicity and of activitywhich are posed for the preparation of veterinary preparationscomprising a peptide or a molecule possessing a glutamic acid or aglutamine at their N-terminal end may be solved using addition saltswith strong acids to stabilize said peptides or molecules.

[0039] Among the pharmaceutical compositions according to the invention,a preferred composition consists of a vaccine, characterized in that itcomprises at least one MHC ligand according to the invention, existingin the form of a physiologically acceptable addition salt with a strongacid, as defined above.

[0040] This vaccine may comprise, in addition, at least one adjuvant, inparticular chosen from the salts of Aluminum (Alum) or of Calcium, theenterobacterial OmpA proteins, the tetanus toxoid (TT), the diphtheriatoxoid (DT), CRM197 (cross-reactivity material), PLGA, ISCOM, MontanideISA 720, aliphatic quaternary ammoniums, MPL-A, Quil-A, CpGs, Leif, thecholera toxin (CT), LT (LT for “heat labile enterotoxin”) or thedetoxified versions of CT or LT.

[0041] In a preferred form of the invention, the vaccine comprises, inaddition, a carrier compound mixed with or coupled to said ligand.

[0042] Preferably, said carrier compound is chosen from the peptidegroup comprising toxoids, in particular the diphtheria toxoid (DT) orthe tetanus toxoid (TT), proteins derived from streptococcus (such asthe human seralbumin binding protein, called “BB”, described inWO96/14415), membrane proteins OmpA (for “outer membrane protein type A”and the outer membrane protein complexes (OMPC), outer membrane vesicles(OMV) or heat-shock proteins (HSP).

[0043] Advantageously, said carrier compound is covalently coupled withthe ligand. The expression “coupling” is intended to designate both acoupling achieved by a chemical route between the two compounds, and abiological coupling, by genetic recombination, as defined below.

[0044] Thus, according to the invention, it is possible to introduce oneor more linking elements, in particular amino acids, in order tofacilitate the coupling reactions between the carrier compound and theantigen or hapten, in particular. when they are of a peptide nature, itbeing possible for the covalent coupling of the antigen or hapten to becarried out at the N- or C-terminal end of the carrier compound.

[0045] The bifunctional reagents allowing this coupling are determinedaccording to the end of the carrier compound chosen and the nature ofthe antigen or hapten to be coupled. These coupling techniques are wellknown to persons skilled in the art.

[0046] The conjugates derived from a coupling of peptides may also beprepared by genetic recombination. The hybrid peptide (conjugate) mayindeed be produced by recombinant DNA techniques by insertion into oraddition to the DNA sequence encoding the carrier compound, of asequence encoding the antigenic, immunogenic or hapten peptide orpeptides. These techniques for preparing a hybrid peptide by geneticrecombination are well known to persons skilled in the art (cf. forexample Makrides, 1996, Microbiologicals Reviews, 60, 512-538).

[0047] Preferably, said carrier compound is a protein derived fromstreptococcus or a membrane protein OmpA from an enterobacterium, inparticular from Klebsiella pneumoniae, or one of its fragments.

[0048] The ligand according to the invention, optionally combined with acarrier compound, may be incorporated into vectors chosen fromliposomes, virosomes, nanospheres, microspheres, microcapsules orbiovectors. Persons skilled in the art know how to choose theappropriate vector according to the desired aim (protection of theligand optionally combined with a carrier compound or an adjuvant forthe degradation, targeting of cells of interest, search for penetrationof the material contained in the vector inside target cells, and thelike).

[0049] One embodiment of the invention comprises in particular ananti-melanoma vaccine, characterized in that it comprises at least onepeptide ELAGIGILTV (SEQ ID No. 81) in hydrochloride or sulfate form.

[0050] The subject of another embodiment is an anti-melanoma vaccine,characterized in that it comprises at least one peptide ELAGIGILTV (SEQID No. 81) in hydrochloride or sulfate form and, in addition, anenterobacterial OmpA protein.

[0051] It is also possible to develop vaccines according to theinvention for use in the veterinary field, it being possible for theidentical problems of structural instability, preservation over time,toxicity and activity to be solved in the same manner.

[0052] The subject of the invention is also a method for the in vitrodiagnosis of pathologies associated with the presence, in a patient'sbody, of MHC ligands which can interact with MHC molecules, and whichmay be directly or indirectly involved in the process of development ofthese pathologies in humans or animals, characterized in that itcomprises the steps of:

[0053] bringing a biological sample obtained from a patient, inparticular blood or any biological sample which may contain lymphocytes,into contact with an MHC ligand according to the invention, underconditions allowing the formation of a binary complex between said MHCligand and the MHC molecules present in said sample, and the reactionbetween said binary complex and the T cell receptors which may bepresent in said biological sample,

[0054] detecting in vitro the ternary complex MHC—MHC ligand—T receptor,which may be formed i the preceding step.

[0055] The diagnostic methods according to the invention areadvantageously carried out in the following manner:

[0056] incubation of said biological sample with MHC ligands accordingto the invention, said MHC ligands being attached to a solid support, inparticular inside wells of microtiter plates of the type normally usedfor carrying out detection or assay techniques well known under the nameELISA (Enzyme Linked Immuno Sorbent Assay),

[0057] incubation of the components attached to the solid support, afteran optional rinsing step, with a medium containing antibodies, inparticular anti-ternary complex antibodies according to the invention,labeled (in particular radioactively, enzymatically or by fluorescence),or which may be recognized in turn by a labeled reagent,

[0058] detection of the labeled antibodies which have remainedrespectively attached to the ternary complexes during the precedingincubation step.

[0059] Rinsing steps are advantageously carried out between thedifferent steps of this method. Persons skilled in the art know how todefine the various incubation conditions, as well as the methods fordetecting MHC—MHC ligand—T receptor complexes, the use of antibodiesbeing only one method among others.

[0060] The subject of the invention is also the packs or kits forcarrying out in vitro diagnostic methods as described above, comprising:

[0061] an MHC ligand according to the invention;

[0062] optionally reagents to allow the formation of an immunologicalreaction between said ligand, the MHC molecules and the T cell receptorswhich may be present in the biological sample;

[0063] optionally reagents which make it possible to detect the ternarycomplex according to the invention, which was produced at the end of theimmunological reaction, said reagents optionally containing a marker orbeing capable of being recognized in turn by a labeled reagent, moreparticularly in the case where the peptide analog is not labeled.

[0064] In particular, the use of the peptides ELAGIGILTV (SEQ ID No.81), EAAGIGILTV (SEQ ID No. 112), EADPTGHSY (SEQ ID No. 2), or EVDPIGHLY(SEQ ID No. 273) is preferred in a method for the diagnosis of amelanoma. The peptides QVPLRPMTYK (SEQ ID No. 567), EIYKRWIIL (SEQ IDNo. 10), and EIKDTKEAL (SEQ ID No. 692) may be used in a method for thediagnosis of an HIV infection.

[0065] The use of a ligand according to the invention, for thepreparation of a vaccine intended for the prophylactic or therapeutictreatment of viral, bacterial, parasitic or fungal infections, isanother subject of the invention.

[0066] The invention also relates to the use of a ligand according tothe invention for the preparation of a vaccine intended for theprophylactic or therapeutic treatment of cancers, and preferably forinhibiting the growth of tumors.

[0067] The present invention also relates to the use of aphysiologically acceptable strong acid for stabilizing and maintainingthe biological activity of a molecule of pharmaceutical interestcontaining a glutamic acid or a glutamine at its N-terminal end.

[0068] In the preferred case where the molecule of pharmaceuticalinterest is an MHC ligand, the activity which it is sought to maintainis an activity of stimulation and of interaction with the cells of theimmune system.

[0069] The invention also relates to the use of a strong acid forreducing and/or suppressing the formation of the pyroglutamic derivativeof a molecule of pharmaceutical interest containing a glutamic acid or aglutamine at its N-terminal end.

[0070] Likewise, the present invention relates to a method forstabilizing a molecule of pharmaceutical interest containing a glutamicacid or a glutamine at its N-terminal end, characterized in that saidmolecule is reacted with a strong acid under conditions which make itpossible to obtain said molecule in the form of a physiologicallyacceptable addition salt with a strong acid. The reaction with thestrong acid is carried out in particular according to a method asdefined below, it being possible for the strong acid to be chosen fromthe strong acids defined above, and makes it possible to obtainpreferably a hydrochloride.

[0071] Indeed, the invention also relates to a method for preparing amolecule of pharmaceutical interest containing a glutamic acid or aglutamine at its N-terminal end in the form of a physiologicallyacceptable addition salt with a strong acid according to the invention.

[0072] This method may comprise in particular a step of purifying byRP-HPLC said molecule from the corresponding trifluoroacetate salt usingan eluent based on said strong acid, optionally followed by a step offreeze-drying the solution thus obtained.

[0073] An alternative method comprises a step of dissolving atrifluoroacetate salt of said molecule in a solution of said strong acidin excess, optionally followed by a step of freeze-drying the solutionthus obtained.

[0074] It is also possible to carry out the a method according to theinvention which comprises an ion-exchange chromatography step startingwith the corresponding trifluoroacetate salt of said molecule ofpharmaceutical interest, after dissolving said salt in a solutioncontaining said strong acid. The freeze-drying of the product obtainedis also optional.

[0075] In all these applications, an MHC ligand, in particular SEQ IDNo. 81, 112, 2, 273, 567, 10, 692, 11, 464, 466, 106, 257 or 568, ispreferred. More preferably, it is SEQ ID No. 81 and the strong acid saltis a hydrochloride.

[0076] The examples which follow are intended to illustrate someembodiments of the invention and should not be considered as limitingthe field of the invention.

DESCRIPTION OF THE FIGURES

[0077]FIG. 1: Difference in cell lysis of the EL-4 A2/Kb cells prepulsedwith the ELA peptide, by lymphocytes obtained after immunization of micewith the ELA (diamonds) or AcELA (squares) peptides in the presence ofthe adjuvant protein rP40, according to the protocol of example III.

[0078]FIG. 2: Generation of CTL after immunization, with the peptidesELA (trifluoroacetate, 2.A), ELA (hydrochloride, 2.B) or PyrELA(trifluoroacetate, 2.C) in the presence of the adjuvant protein rP40,according to the protocol of example IV.

[0079]FIG. 3: Chromatogram of the ELA peptide in acetate (3.A) orhydrochloride (3.B) form, stored at 37° C. for two months.

[0080]FIG. 4: Chromatogram of the ELA peptide in hydrochloride forminitially (4.A) or after one month of storage at 4° C. (4.B).

EXAMPLES Example I Synthesis of the Peptides ELA, PyrELA and ACELA

[0081] Peptide ELA: the peptide ELA (SEQ ID No. 81) is synthesized in asolid phase from the C-terminal amino acid toward the N-terminal aminoacid (glutamic acid) in FMOC or tBOC chemistry. After cleavage of theresin and of the groups protecting the reactive side chains, the peptideis purified in a conventional manner with eluents based ontrifluoroacetic acid/water and trifluoroacetic acid/acetonitrile beforebeing freeze-dried. The purity of the peptide is checked byreversed-phase liquid chromatography. The amino acid composition ischecked after hydrolysis and assay of the derived amino acids obtained.The exact mass is measured by mass spectrometry.

[0082] Peptide PyrELA: the peptide PyrELA is synthesized in the samemanner as the peptide ELA, the only difference being the coupling of thelast N-terminal amino acid: the glutamic acid is replaced by apyroglutamic acid.

[0083] Peptide AcELA: the peptide AcELA is synthesized in the samemanner as the peptide ELA, the only difference being a capping of theglutamic acid with the aid of acetic anhydride.

Example II Preparation of a Hydrochloride Salt

[0084] II.A: Method A

[0085] Starting with the corresponding trifluoroacetate salt, apurification is carried out by RP-HPLC with the aid of an eluent Acomposed of water containing 0.1% HCl and an eluent B composed of 80%acetonitrile and 20% water containing 0.1% HCl.

[0086] A conventional freeze-drying step is then carried out.

[0087] II.B: Method B

[0088] Starting with the corresponding trifluoroacetate salt,dissolution is carried out in a solution with an excess of HCl andstirring is maintained for 2 hours. It is also possible to use anorganic aqueous solution of the peptide in which HCl in gaseous form isbubbled.

[0089] A conventional freeze-drying step is then carried out.

[0090] II.C: Method C

[0091] his reaction is carried out starting with the correspondingtrifluoroacetate salt, with the aid of an ion-exchange chromatography.

[0092] Commercially available ion-exchange resins in the hydrochlorideform are used (Resin Dowex 1×4, Amberlite IRA 416), which can be used assuch once regenerated.

[0093] a) Regeneration of the resin: the resin to be regenerated isintroduced into a large column equipped with sintered glass of highporosity (1 or 2). The resin is then successively washed with ultra-purewater (pH 5-6), with 1N sodium hydroxide (pH 14), with ultra-pure water(pH 7), with 1N HCl (pH 1) and once again with ultra-pure water (pH5-6). The resin is stored in an acetonitrile/10⁻⁴ N HCl (20/80) mixtureat room temperature for at least one year.

[0094] b) Anion exchange (trifluoroacetate=>chloride): the peptide isdissolved in a 10⁻⁴ N HCl/acetonitrile solution, with a proportion ofacetonitrile which may vary from 0 to 80%). The solution is injected atthe top of the column. The peptide is eluted with the dissolutionsolution. The fractions containing the product are combined before beingfreeze-dried.

[0095] The quantity of hydrochloride may be assayed by an anion-exchangechromatography. The quantity of trifluoroacetic acid may be assayed bygas chromatography.

Example III Generation of anti-Melan-A CTL after Immunization with rP40Mixed with ELA or ACELA

[0096] Transgenic mice HLA-A* 0201/Kb (A2/Kb) of the strainC57B1/6×BDA/2 were used in this study (Vitiello et al., 1991, J. Exp.Med., 173, 1007). The MHC class I molecule expressed in these mice is achimeric molecule formed of the a1 and a2 domains of the human moleculeHLA-A0201 (allotype most frequently found) and of the a3 domain of themurine molecuke K^(b).

[0097] A2/Kb mice received 300 μg of rP40 mixed with 50 μg of ELA or 300μg of rP40 mixed with 50 μg of AcELA.

[0098] a) Generation of Effector Cytotoxic Cells:

[0099] 10 days after immunization, the mice are sacrificed and thelymphocytes of the draining ganglia are recovered so as to be stimulatedin vitro with the relevant peptide. These lymphocytes (4-5×10⁶) arecultured in a 24-well plate in DMEM plus 10 mM HEPES, 10% FCS and 50 μmβ-2-mercaptoethanol with 2-5×10⁵ EL-4 A2/Kb cells (murine cellstransfected with the HLA-A* 0201/Kb gene) which have been irradiated (10kRads) and prepulsed for 1 h at 37° C. with 1 μM of the relevantpeptide. After two weekly stimulations, the cells are tested for theircytotoxic activity.

[0100] b) Measurement of the Cytotoxic Activity:

[0101] The EL-4 A2/Kb cells are incubated for 1 h with ⁵¹Cr in thepresence or otherwise of ELA, washed and then coincubated with theeffector cells in various ratios in a 96-well plate in a volume of 200μl for 4 to 6 h at 37° C. The cells are then centrifuged and the releaseof ⁵¹Cr is measured in 100 μl of supernatant. The percentage of specificlysis is calculated as follows:

% lysis=(experimental release−spontaneous release)/ (totalrelease−spontaneous release)×100

% specific lysis=% lysis with cells pulsed with the peptide−% lysis withcells not pulsed with the peptide.

[0102] The difference in cell lysis observed for the ELA (diamonds) andAcELA (squares) peptides in the presence of the adjuvant protein rP40(I. Rauly et al., Infect. Immun., 1999, 67, 5547) is represented in FIG.1.

[0103] c) Conclusion:

[0104] Whereas an anti-ELA CTL activity is observed after immunizationof mice with P40/ELA, no CTL activity is measured when the mice wereimmunized with P40/AcELA. These results indicate that the CTLs generatedby AcELA do not recognize the native ELA peptide.

Comparative Example IV CTL Activity of the Peptides ELA, PyrELA andACELA

[0105] A2/Kb mice received:

[0106] 300 μg of rP40 mixed with 50 μg of ELA (Trifluoroacetate)

[0107] 300 μg of rP40 mixed with 50 μg of ELA (Hydrochloride)

[0108] 300 μg of rP40 mixed with 50 μg of PyrELA (Trifluoroacetate)

[0109] a) Generation of Effector Cytotoxic Cells:

[0110] 10 days after immunization, the mice are sacrificed and thelymphocytes of the draining ganglia are recovered so as to be stimulatedin vitro with the relevant peptide. These lymphocytes (4-5×10⁶ ) arecultured in a 24-well plate in DMEM plus 10 mM HEPES, 10% FCS and 50 μmβ-2-mercaptoethanol with 2-5×10⁵ EL-4 A2/Kb cells (murine cellstransfected with the HLA-A* 0201/Kb gene) which have been irradiated (10kRads) and prepulsed for 1 h at 37° C. with 1 μM of the relevantpeptide. After two weekly stimulations, the cells are tested for theircytotoxic activity.

[0111] b) Measurement of the Cytotoxic Activity:

[0112] The EL-4 A2/Kb cells are incubated for 1 h with ⁵¹Cr in thepresence or otherwise of ELA, washed and then coincubated with theeffector cells in various ratios in a 96-well plate in a volume of 200μl for 4 to 6 h at 37° C. The cells are then centrifuged and the releaseof ⁵¹Cr is measured in 100 μl of supernatant. The percentage of specificlysis is calculated as follows:

% lysis=(experimental release−spontaneous release)/ (totalrelease−spontaneous release)×100

% specific lysis=% lysis with cells pulsed with the peptide−% lysis withcells not pulsed with the ELA peptide.

[0113] c) The Generation of Anti-Melan-A CTL after Immunization withrP40 mixed with the Peptides ELA (Trifluoroacetate), ELA (Hydrochloride)or PyrELA (Trifluoroacetate) is represented in FIG. 2.

[0114] d) Conclusions:

[0115] 1. Whereas an anti-ELA CTL activity is observed afterimmunization of mice with P40/ELA (Trifluoroacetate), no CTL activity ismeasured when the mice were immunized with P40/PyrELA(Trifluoroacetate). These results indicate that the CTLs generated byPyrELA do not recognize the native ELA peptide.

[0116] 2. Surprisingly, the immunization with P40/ELA (Hydrochloride) isas effective as that with P40/ELA (Trifluoroacetate) for generating ananti-ELA CTL response.

Example V Studies of Accelerated Stability of the Acetate andHydrochloride Forms of the ELA Peptide

[0117] The peptides are analyzed by reversed-phase HPLC with the aid ofan eluent A composed of water containing 0.1% TFA and an eluent Bcomposed of 80% acetonitrile and 20% water containing 0.1% TFA.

[0118]FIG. 3 shows the chromatograms for the ELA peptide in acetate(3.A) or hydrochloride (3.B) form stored at 37° C. for 2 months.

[0119] Conclusion:

[0120] In the acetate form, the degradation of the ELA peptide to aninactive cyclized peptide PyrELA after 2 months at 37° C. is 53%.Surprisingly, in the hydrochloride form, it is only 10%.

Example VI Stability of the ELA Peptide in the Hydrochloride Form Storedat 4° C.

[0121]FIG. 4 shows a chromatogram for the ELA peptide in thehydrochloride form at t=0: (98.9% of ELA and 0.4% of PyrELA; FIG. 4.A)and after one month of storage at 4° C. (98.8% of ELA and 0.5% ofPyrELA; FIG. 4.B).

[0122] Conclusion:

[0123] Surprisingly, the ELA peptide in the hydrochloride form isextremely stable at 4° C. It can therefore be easily handled and storedat a temperature of 4 or −20° C. That is not the case for an equivalentpeptide (MART 3), prepared in the acetate form which must be stored at−80° C. (M. Marchand et al., Int. J. Cancer, 1999, 80, 219).

[0124] The strong acid saline form therefore allows a much easierstorage at 4° C. (refrigerator) or at −20° C. (freezer) with totalphysicochemical stability, as shown by the examples above.

1 697 1 15 PRT Human immunodeficiency virus 1 Glu Ala Ala Glu Trp AspArg Val His Pro Val His Ala Gly Pro 1 5 10 15 2 9 PRT Homo sapiens 2 GluAla Asp Pro Thr Gly His Ser Tyr 1 5 3 17 PRT Homo sapiens 3 Glu Ile LysIle Leu Asn Ile Phe Gly Val Ile Lys Gly Phe Val Glu 1 5 10 15 Pro 4 9PRT Homo sapiens 4 Glu Ile Leu Gly Phe Val Phe Thr Leu 1 5 5 10 PRTHuman immunodeficiency virus 5 Glu Ile Leu Lys Glu Pro Val His Gly Val 15 10 6 9 PRT Homo sapiens 6 Glu Ile Met Lys Trp Asn Arg Glu Arg 1 5 7 25PRT Human immunodeficiency virus type 1 7 Glu Ile Gln Lys Gln Gly GlnGly Gln Trp Thr Tyr Gln Ile Tyr Gln 1 5 10 15 Glu Pro Phe Lys Asn LeuLys Thr Gly 20 25 8 9 PRT Homo sapiens Xaa = any amino acid 8 Glu IleVal Asp Xaa Xaa Glu Lys Val 1 5 9 8 PRT Homo sapiens 9 Glu Ile Tyr LysArg Trp Ile Ile 1 5 10 9 PRT Human immunodeficiency virus 10 Glu Ile TyrLys Arg Trp Ile Ile Leu 1 5 11 21 PRT Homo sapiens 11 Glu Lys Ala GlyGly Ala Gln Leu Gly Val Met Gln Gly Pro Met Gly 1 5 10 15 Pro Met GlyPro Arg 20 12 16 PRT Rabies virus 12 Glu Lys Asp Asp Leu Ser Val Glu AlaGlu Ile Ala His Gln Ile Ala 1 5 10 15 13 9 PRT Homo sapiens 13 Glu AlaAsp Pro Thr Ser Asn Thr Tyr 1 5 14 17 PRT Plasmodium malariae 14 Glu LysAsp Ile Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 1514 PRT Streptococcus sp 15 Glu Lys Asp Ile Gln Phe Gly Arg Glu Val HisAla Ala Asp 1 5 10 16 17 PRT Streptococcus sp 16 Glu Lys Asp Ile Gln PheGly Arg Glu Val His Ala Ala Asp Leu Leu 1 5 10 15 Arg 17 25 PRTStreptococcus sp 17 Glu Lys Asp Ile Gln Phe Gly Arg Glu Val His Ala AlaAsp Leu Leu 1 5 10 15 Arg His Lys Gln Glu Ile Ala Glu Lys 20 25 18 14PRT Human immunodeficiency virus 18 Glu Lys Gly Gly Leu Glu Gly Leu IleHis Ser Gln Arg Arg 1 5 10 19 17 PRT Plasmodium malariae 19 Glu Lys GlyIle Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 20 14PRT Homo sapiens 20 Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His GlnGly 1 5 10 21 16 PRT Homo sapiens 21 Glu Lys His Lys Val Tyr Ala Cys GluVal Thr His Gln Gly Leu Ser 1 5 10 15 22 17 PRT Homo sapiens 22 Glu LysHis Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 1 5 10 15 Ser 2317 PRT Plasmodium malariae 23 Glu Lys Lys Asp Ala Lys Met Glu Lys AlaSer Ser Val Phe Asn Val 1 5 10 15 Val 24 15 PRT Homo sapiens 24 Glu AlaGlu Gln Leu Arg Ala Tyr Leu Asp Gly Thr Gly Val Glu 1 5 10 15 25 17 PRTPlasmodium malariae 25 Glu Lys Lys Gly Ala Lys Met Glu Lys Ala Ser SerVal Phe Asn Val 1 5 10 15 Val 26 17 PRT Plasmodium malariae 26 Glu LysLys Ile Ala Asp Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 2717 PRT Plasmodium malariae 27 Glu Lys Lys Ile Ala Phe Met Glu Lys AlaSer Ser Val Phe Asn Val 1 5 10 15 Val 28 17 PRT Plasmodium malariae 28Glu Lys Lys Ile Ala Gly Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 1015 Val 29 17 PRT Plasmodium malariae 29 Glu Lys Lys Ile Ala Lys Asp GluLys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 30 17 PRT Plasmodiummalariae 30 Glu Lys Lys Ile Ala Lys Gly Glu Lys Ala Ser Ser Val Phe AsnVal 1 5 10 15 Val 31 17 PRT Plasmodium malariae 31 Glu Lys Lys Ile AlaLys Lys Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 32 17 PRTPlasmodium malariae 32 Glu Lys Lys Ile Ala Lys Met Glu Asp Ala Ser SerVal Phe Asn Val 1 5 10 15 Val 33 17 PRT Plasmodium malariae 33 Glu LysLys Ile Ala Lys Met Glu Phe Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 3417 PRT Plasmodium malariae 34 Glu Lys Lys Ile Ala Lys Met Glu Gly AlaSer Ser Val Phe Asn Val 1 5 10 15 Val 35 13 PRT Mycobacterium leprae 35Glu Ala Phe Val Val Glu Phe Asp Leu Pro Gly Ile Lys 1 5 10 36 17 PRTPlasmodium malariae 36 Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Glu SerVal Phe Asn Val 1 5 10 15 Val 37 17 PRT Plasmodium malariae 37 Glu LysLys Ile Ala Lys Met Glu Lys Ala Phe Ser Val Phe Asn Val 1 5 10 15 Val 3817 PRT Plasmodium malariae 38 Glu Lys Lys Ile Ala Lys Met Glu Lys AlaLys Ser Val Phe Asn Val 1 5 10 15 Val 39 17 PRT Plasmodium malariae 39Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser Glu Val Phe Asn Val 1 5 1015 Val 40 17 PRT Plasmodium malariae 40 Glu Lys Lys Ile Ala Lys Met GluLys Ala Ser Phe Val Phe Asn Val 1 5 10 15 Val 41 17 PRT Plasmodiummalariae 41 Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser Lys Val Phe AsnVal 1 5 10 15 Val 42 17 PRT Plasmodium malariae 42 Glu Lys Lys Ile AlaLys Met Glu Lys Ala Ser Ser Asp Phe Asn Val 1 5 10 15 Val 43 17 PRTPlasmodium malariae 43 Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser SerGly Phe Asn Val 1 5 10 15 Val 44 17 PRT Plasmodium malariae 44 Glu LysLys Ile Ala Lys Met Glu Lys Ala Ser Ser Lys Phe Asn Val 1 5 10 15 Val 4517 PRT Plasmodium malariae 45 Glu Lys Lys Ile Ala Lys Met Glu Lys AlaSer Ser Val Asp Asn Val 1 5 10 15 Val 46 19 PRT Homo sapiens 46 Glu AlaGly Ala Pro Gly Leu Val Gly Pro Arg Gly Glu Arg Gly Phe 1 5 10 15 ProGly Glu 47 17 PRT Plasmodium malariae 47 Glu Lys Lys Ile Ala Lys Met GluLys Ala Ser Ser Val Phe Glu Val 1 5 10 15 Val 48 17 PRT Plasmodiummalariae 48 Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser Ser Val Phe PheVal 1 5 10 15 Val 49 17 PRT Plasmodium malariae 49 Glu Lys Lys Ile AlaLys Met Glu Lys Ala Ser Ser Val Phe Lys Val 1 5 10 15 Val 50 17 PRTPlasmodium malariae 50 Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser SerVal Phe Asn Asp 1 5 10 15 Val 51 17 PRT Plasmodium malariae 51 Glu LysLys Ile Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Gly 1 5 10 15 Val 5217 PRT Plasmodium malariae 52 Glu Lys Lys Ile Ala Lys Met Glu Lys AlaSer Ser Val Phe Asn Lys 1 5 10 15 Val 53 17 PRT Plasmodium malariae 53Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 1015 Val 54 19 PRT Plasmodium malariae 54 Glu Lys Lys Ile Ala Lys Met GluLys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val Asn Ser 55 17 PRTPlasmodium malariae 55 Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser SerVal Gly Asn Val 1 5 10 15 Val 56 17 PRT Plasmodium malariae 56 Glu LysLys Ile Ala Lys Met Glu Lys Ala Ser Ser Val Lys Asn Val 1 5 10 15 Val 5720 PRT Homo sapiens 57 Glu Ala Gly His Gln Lys Val Val Phe Tyr Ile LeuIle Gln Arg Lys 1 5 10 15 Pro Leu Phe Tyr 20 58 17 PRT Plasmodiummalariae 58 Glu Lys Lys Ile Ala Lys Met Glu Lys Asp Ser Ser Val Phe AsnVal 1 5 10 15 Val 59 17 PRT Plasmodium malariae 59 Glu Lys Lys Ile AlaLys Met Glu Lys Glu Ser Ser Val Phe Asn Val 1 5 10 15 Val 60 17 PRTPlasmodium malariae 60 Glu Lys Lys Ile Ala Lys Met Glu Lys Val Ser SerVal Phe Asn Val 1 5 10 15 Val 61 17 PRT Plasmodium malariae 61 Glu LysLys Ile Ala Lys Met Glu Lys Tyr Ser Ser Val Phe Asn Val 1 5 10 15 Val 6217 PRT Plasmodium malariae 62 Glu Lys Lys Ile Ala Lys Met Phe Lys AlaSer Ser Val Phe Asn Val 1 5 10 15 Val 63 17 PRT Plasmodium malariae 63Glu Lys Lys Ile Ala Lys Met Gly Lys Ala Ser Ser Val Phe Asn Val 1 5 1015 Val 64 17 PRT Plasmodium malariae 64 Glu Lys Lys Ile Ala Lys Met LysLys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 65 17 PRT Plasmodiummalariae 65 Glu Lys Lys Ile Ile Lys Met Glu Lys Ala Ser Ser Val Phe AsnVal 1 5 10 15 Val 66 17 PRT Plasmodium malariae 66 Glu Lys Lys Ile LysLys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 67 17 PRTPlasmodium malariae 67 Glu Lys Lys Ile Val Lys Met Glu Lys Ala Ser SerVal Phe Asn Val 1 5 10 15 Val 68 11 PRT Homo sapiens 68 Glu Ala Ile IleHis Val Leu His Ser Arg His 1 5 10 69 17 PRT Plasmodium malariae 69 GluLys Lys Ile Tyr Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15Val 70 17 PRT Plasmodium malariae 70 Glu Lys Lys Lys Ala Lys Met Glu LysAla Ser Ser Val Phe Asn Val 1 5 10 15 Val 71 13 PRT Homo sapiens 71 GluLys Lys Tyr Phe Ala Ala Thr Gln Phe Glu Pro Leu 1 5 10 72 17 PRT Homosapiens 72 Glu Lys Lys Tyr Phe Ala Ala Thr Gln Phe Glu Pro Leu Ala AlaArg 1 5 10 15 Leu 73 13 PRT Streptococcus sp 73 Glu Lys Leu Ala Lys GlnAla Glu Glu Leu Ala Lys Leu 1 5 10 74 21 PRT Streptococcus sp 74 Glu LysGln Ile Ser Asp Ala Ser Arg Gln Gly Leu Arg Arg Asp Leu 1 5 10 15 AspAla Ser Arg Glu 20 75 17 PRT Plasmodium malariae 75 Glu Lys Tyr Ile AlaLys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 76 11 PRTInfluenza virus 76 Glu Lys Tyr Val Lys Gln Asn Thr Leu Lys Ala 1 5 10 7713 PRT Homo sapiens 77 Glu Lys Tyr Val Lys Gln Asn Thr Leu Lys Leu AlaThr 1 5 10 78 15 PRT Homo sapiens 78 Glu Leu Ala Ala Ala Met Lys Arg HisGly Leu Asp Asn Tyr Arg 1 5 10 15 79 12 PRT Homo sapiens 79 Glu Ala IleGln Pro Gly Cys Ile Gly Gly Pro Lys 1 5 10 80 10 PRT Humanimmunodeficiency virus 80 Glu Leu Ala Glu Asn Arg Glu Ile Leu Lys 1 5 1081 10 PRT Homo sapiens 81 Glu Leu Ala Gly Ile Gly Ile Leu Thr Val 1 5 1082 15 PRT Homo sapiens 82 Glu Leu Ala Gln Tyr Leu Asp Leu Val Arg AlaLeu Glu Ala Ala 1 5 10 15 83 9 PRT Plasmodium falciparum 83 Glu Leu AspVal Leu Lys Lys Leu Val 1 5 84 15 PRT Plasmodium falciparum 84 Glu LeuAsp Tyr Ala Asn Asp Ile Glu Lys Lys Ile Cys Lys Met 1 5 10 15 85 15 PRTHomo sapiens 85 Glu Leu Phe Arg Lys Asp Ile Ala Ala Lys Tyr Lys Glu GlyTyr 1 5 10 15 86 18 PRT Homo sapiens 86 Glu Leu Phe Arg Lys Asp Ile AlaAla Lys Tyr Lys Glu Leu Gly Tyr 1 5 10 15 Gly Lys 87 12 PRT Homo sapiens87 Glu Leu Gly Gly Trp Lys Leu Lys Leu Gln Ser Asp 1 5 10 88 9 PRTClostridium tetani 88 Glu Leu Ile His Val Leu His Gly Leu 1 5 89 9 PRTNewcastle disease virus 89 Glu Leu Ile His Val Asn His Leu Ile 1 5 90 13PRT Homo sapiens 90 Glu Ala Ile Tyr Asp Ile Cys Arg Arg Asn Leu Asp Ile1 5 10 91 9 PRT Homo sapiens 91 Glu Leu Ile Arg Val Glu Gly Asn Leu 1 592 9 PRT Mus musculus 92 Glu Leu Ile Arg Val Val His Gln Leu 1 5 93 8PRT Homo sapiens 93 Glu Leu Lys Glu Lys Thr Gln Leu 1 5 94 9 PRT Homosapiens Xaa = any amino acid 94 Glu Leu Lys Glu Lys Xaa Tyr Glu Leu 1 595 9 PRT Homo sapiens Xaa = any amino acid 95 Glu Leu Lys Ile Lys ValTyr Xaa Leu 1 5 96 8 PRT Homo sapiens 96 Glu Leu Lys Lys Lys Thr Asn Leu1 5 97 6 PRT Homo sapiens 97 Glu Leu Lys Leu Lys Gly 1 5 98 9 PRTInfluenza A virus 98 Glu Leu Lys Ser Lys Tyr Trp Ala Ile 1 5 99 9 PRTInfluenza virus 99 Glu Leu Lys Ser Arg Tyr Trp Ala Ile 1 5 100 9 PRTHomo sapiens 100 Glu Leu Lys Val Lys Asn Leu Glu Leu 1 5 101 17 PRT Homosapiens 101 Glu Ala Ile Tyr Asp Ile Cys Arg Arg Asn Leu Asp Ile Glu ArgPro 1 5 10 15 Thr 102 12 PRT Human immunodeficiency virus 102 Glu LeuLeu Gly Ile Trp Gly Cys Ser Gly Lys Leu 1 5 10 103 9 PRT Homo sapiens103 Glu Leu Asn Glu Ala Leu Glu Leu Lys 1 5 104 9 PRT Epstein Barr virus104 Glu Leu Arg Gly Arg Ala Tyr Gly Leu 1 5 105 9 PRT Humanimmunodeficiency virus 105 Glu Leu Arg Ser Leu Tyr Asn Thr Val 1 5 106 9PRT Influenza virus 106 Glu Leu Arg Ser Arg Tyr Trp Ala Ile 1 5 107 9PRT Homo sapiens Xaa = any amino acid 107 Glu Leu Val Asp Xaa Xaa GluLys Val 1 5 108 9 PRT Homo sapiens 108 Glu Leu Val His Phe Leu Leu LeuLys 1 5 109 10 PRT Human immunodeficiency virus 109 Glu Leu Val Asn GlnIle Ile Glu Gln Leu 1 5 10 110 9 PRT Homo sapiens 110 Glu Leu Val SerGlu Phe Ser Arg Met 1 5 111 9 PRT Homo sapiens 111 Glu Leu Val Ser GluPhe Ser Arg Val 1 5 112 10 PRT Homo sapiens 112 Glu Ala Ala Gly Ile GlyIle Leu Thr Val 1 5 10 113 17 PRT Homo sapiens 113 Glu Ala Lys Pro GlyLys Ala Gly Glu Arg Gly Pro Pro Gly Pro Gln 1 5 10 15 Gly 114 9 PRT Homosapiens 114 Glu Leu Val Ser Glu Val Ser Lys Val 1 5 115 19 PRT Humanimmunodeficiency virus 115 Glu Leu Tyr Pro Leu Thr Ser Leu Arg Ser LeuPhe Gly Asn Asp Pro 1 5 10 15 Ser Ser Gln 116 9 PRT Homo sapiens 116 GluMet Phe Arg Glu Leu Asn Glu Ala 1 5 117 8 PRT Homo sapiens 117 Glu AsnAla Ala Phe Val Leu Leu 1 5 118 15 PRT Homo sapiens 118 Glu Asn Ala ValVal His Phe Phe Lys Asn Ile Val Thr Pro Arg 1 5 10 15 119 15 PRTPlasmodium falciparum 119 Glu Asn Asp Ile Glu Lys Lys Ile Cys Lys MetGlu Lys Cys Ser 1 5 10 15 120 23 PRT Homo sapiens 120 Glu Asn Gly GluTrp Ala Ile Gln His Arg Pro Ala Lys Met Leu Leu 1 5 10 15 Asp Pro AlaAla Pro Ala Gln 20 121 12 PRT Homo sapiens 121 Glu Asn Ile Glu Phe LeuGlu Asp Thr Asp Met Lys 1 5 10 122 18 PRT Homo sapiens 122 Glu Asn IleGlu Phe Leu Glu Asp Thr Asp Met Lys Ser Leu Glu Asn 1 5 10 15 Lys Ser123 8 PRT Homo sapiens 123 Glu Asn Ile Phe Tyr Cys Pro Ile 1 5 124 13PRT Streptococcus sp 124 Glu Ala Leu Ala Lys Gln Ala Glu Glu Leu Ala LysLeu 1 5 10 125 15 PRT Homo sapiens 125 Glu Asn Pro Ala Val His Phe PheLys Asn Ile Val Thr Pro Arg 1 5 10 15 126 15 PRT Homo sapiens 126 GluAsn Pro Val Ala His Phe Phe Lys Asn Ile Val Thr Pro Arg 1 5 10 15 127 15PRT Homo sapiens 127 Glu Asn Pro Val Lys His Phe Phe Lys Asn Ile Val ThrPro Arg 1 5 10 15 128 15 PRT Homo sapiens 128 Glu Asn Pro Val Val AlaPhe Phe Lys Asn Ile Val Thr Pro Arg 1 5 10 15 129 15 PRT Homo sapiens129 Glu Asn Pro Val Val Asp Phe Phe Lys Asn Ile Val Thr Pro Arg 1 5 1015 130 15 PRT Homo sapiens 130 Glu Asn Pro Val Val His Ala Phe Lys AsnIle Val Thr Pro Arg 1 5 10 15 131 15 PRT Homo sapiens 131 Glu Asn ProVal Val His Phe Ala Lys Asn Ile Val Thr Pro Arg 1 5 10 15 132 15 PRTHomo sapiens 132 Glu Asn Pro Val Val His Phe Phe Ala Asn Ile Val Thr ProArg 1 5 10 15 133 15 PRT Homo sapiens 133 Glu Asn Pro Val Val His PhePhe Lys Ala Ile Val Thr Pro Arg 1 5 10 15 134 15 PRT Homo sapiens 134Glu Asn Pro Val Val His Phe Phe Lys Asn Ala Val Thr Pro Arg 1 5 10 15135 15 PRT Homo sapiens 135 Glu Ala Leu Ile His Gln Leu Lys Ile Asn ProTyr Val Leu Ser 1 5 10 15 136 15 PRT Homo sapiens 136 Glu Asn Pro ValVal His Phe Phe Lys Asn Ile Ala Thr Pro Arg 1 5 10 15 137 15 PRT Homosapiens 137 Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Ala Thr Pro Arg1 5 10 15 138 15 PRT Homo sapiens 138 Glu Asn Pro Val Val His Phe PheLys Asn Ile Val Ala Pro Arg 1 5 10 15 139 14 PRT Homo sapiens 139 GluAsn Pro Val Val His Phe Phe Lys Asn Ile Val Thr Ala 1 5 10 140 15 PRTHomo sapiens 140 Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr AlaArg 1 5 10 15 141 15 PRT Homo sapiens 141 Glu Asn Pro Val Val His PhePhe Lys Asn Ile Val Thr Pro Ala 1 5 10 15 142 15 PRT Homo sapiens 142Glu Asn Pro Val Val His Phe Phe Lys Asn Ile Val Thr Pro Arg 1 5 10 15143 19 PRT Homo sapiens 143 Glu Asn Pro Val Val His Phe Phe Lys Asn IleVal Thr Pro Arg Thr 1 5 10 15 Pro Pro Tyr 144 15 PRT Homo sapiens 144Glu Asn Pro Val Val His Phe Phe Arg Asn Ile Val Thr Pro Arg 1 5 10 15145 15 PRT Homo sapiens 145 Glu Asn Pro Val Val His Tyr Phe Lys Asn IleVal Thr Pro Arg 1 5 10 15 146 12 PRT Homo sapiens 146 Glu Ala Leu ValArg Gln Gly Leu Ala Lys Val Ala 1 5 10 147 15 PRT Homo sapiens 147 GluAsn Pro Val Val Lys Phe Phe Lys Asn Ile Val Thr Pro Arg 1 5 10 15 148 9PRT Plasmodium falciparum 148 Glu Pro Ala Pro Phe Asp Glu Thr Leu 1 5149 14 PRT Homo sapiens 149 Glu Pro Asp His Tyr Val Val Val Gly Ala GlnArg Asp Ala 1 5 10 150 20 PRT Homo sapiens 150 Glu Pro Glu Ala Ser ProSer Leu Trp Glu Ile Glu Phe Ala Lys Gln 1 5 10 15 Leu Ala Ser Val 20 15114 PRT Homo sapiens 151 Glu Pro Glu Ile Thr Ile Leu Asn Val Lys Leu GlnPro Ala 1 5 10 152 9 PRT Human immunodeficiency virus 152 Glu Pro GluPro His Ile Leu Leu Phe 1 5 153 11 PRT Human immunodeficiency virus 153Glu Pro Phe Lys Asn Leu Lys Thr Gly Lys Tyr 1 5 10 154 16 PRT Homosapiens 154 Glu Pro Phe Leu Tyr Ile Leu Gly Lys Ser Arg Val Leu Glu AlaGln 1 5 10 15 155 11 PRT Human immunodeficiency virus 155 Glu Pro PheArg Asp Tyr Val Asp Arg Phe Tyr 1 5 10 156 9 PRT Homo sapiens 156 GluPro Gly Pro Val Thr Ala Gln Val 1 5 157 20 PRT Staphylococcus sp 157 GluAla Leu Val Arg Gln Gly Leu Ala Lys Val Ala Tyr Val Tyr Lys 1 5 10 15Pro Asn Asn Thr 20 158 10 PRT Homo sapiens 158 Glu Pro Ile Asp Lys GluIle Tyr Pro Leu 1 5 10 159 8 PRT Human immunodeficiency virus 159 GluPro Ile Asp Lys Glu Leu Tyr 1 5 160 9 PRT Homo sapiens 160 Glu Pro IleLeu Arg Ser Leu Ala Tyr 1 5 161 9 PRT Human immunodeficiency virus 161Glu Pro Ile Val Gly Ala Glu Thr Phe 1 5 162 10 PRT Humanimmunodeficiency virus 162 Glu Pro Ile Val Gly Ala Glu Thr Phe Tyr 1 510 163 9 PRT Homo sapiens 163 Glu Pro Ile Val Gly Ala Glu Thr Ile 1 5164 17 PRT Homo sapiens 164 Glu Pro Lys Asp Phe Val Tyr Ala Leu Asn LeuThr Gln Thr Leu Asn 1 5 10 15 Pro 165 26 PRT Homo sapiens 165 Glu ProLys Ser Gln Asp Ile Tyr Leu Arg Leu Leu Val Lys Leu Tyr 1 5 10 15 ArgPhe Leu Ala Arg Arg Thr Asn Ser Thr 20 25 166 8 PRT Homo sapiens 166 GluPro Lys Tyr Lys Thr Gln Leu 1 5 167 9 PRT Homo sapiens 167 Glu Pro LeuAsp Leu Pro Gln Ile Ile 1 5 168 20 PRT Homo sapiens 168 Glu Ala Leu ValArg Gln Gly Leu Ala Arg Val Ala Tyr Val Tyr Lys 1 5 10 15 Pro Asn AsnThr 20 169 17 PRT Mus musculus 169 Glu Pro Leu Val Pro Leu Asp Asn HisIle Pro Glu Asn Ala Gln Pro 1 5 10 15 Gly 170 9 PRT Humanimmunodeficiency virus 170 Glu Pro Pro Phe Leu Trp Met Gly Tyr 1 5 17115 PRT Homo sapiens 171 Glu Pro Arg Ala Pro Trp Ile Glu Gln Glu Gly ProGlu Tyr Trp 1 5 10 15 172 17 PRT Plasmodium falciparum 172 Glu Pro SerAsp Lys His Ile Glu Gln Tyr Leu Lys Lys Ile Lys Asn 1 5 10 15 Ser 173 8PRT Human immunodeficiency virus 173 Glu Pro Val His Glu Val Tyr Tyr 1 5174 10 PRT Homo sapiens 174 Glu Pro Val Pro Leu Gln Leu Pro Pro Leu 1 510 175 10 PRT Human papillomavirus 175 Glu Pro Tyr Gly Asp Ser Leu PhePhe Tyr 1 5 10 176 10 PRT Homo sapiens 176 Glu Gln Ala Arg Ala Ala ValAsp Thr Tyr 1 5 10 177 11 PRT Sus scrofa 177 Glu Gln Cys Cys Thr Ser IleCys Ser Leu Tyr 1 5 10 178 17 PRT Homo sapiens 178 Glu Gln Asp Phe LeuThr Lys His Ala Ser His Thr Gly Ser Trp Ile 1 5 10 15 Gly 179 20 PRTStaphylococcus aureus 179 Glu Ala Leu Val Arg Gln Gly Leu Ala Arg ValAla Tyr Val Tyr Arg 1 5 10 15 Pro Asn Asn Thr 20 180 31 PRT Clostridiumtetani 180 Glu Gln Asp Pro Ser Gly Ala Thr Thr Lys Ser Ala Met Leu ThrAsn 1 5 10 15 Leu Ile Ile Phe Gly Pro Gly Pro Val Leu Asn Lys Asn GluVal 20 25 30 181 13 PRT Streptococcus sp 181 Glu Gln Leu Ala Lys Gln AlaGlu Glu Leu Ala Lys Leu 1 5 10 182 20 PRT Streptococcus sp 182 Glu GlnLeu Ala Lys Gln Ala Glu Glu Leu Ala Lys Leu Arg Ala Gly 1 5 10 15 LysAla Ser Asp 20 183 16 PRT Human papillomavirus 183 Glu Gln Met Phe ValArg His Leu Phe Asn Arg Ala Gly Thr Val Gly 1 5 10 15 184 15 PRT Humanimmunodeficiency virus 184 Glu Gln Met His Glu Asp Ile Ile Ser Leu TrpAsp Gln Ser Leu 1 5 10 15 185 15 PRT Homo sapiens 185 Glu Gln Asn GlnGlu Gln Arg Arg Ala Ala Gln Arg Ala Ala Gly 1 5 10 15 186 15 PRT Humanimmunodeficiency virus 186 Glu Gln Arg Gly Pro Gly Arg Ala Phe Val ThrIle Gly Lys Ile 1 5 10 15 187 14 PRT Homo sapiens 187 Glu Gln Ser LeuIle Thr Val Glu Gly Asp Lys Ala Ser Met 1 5 10 188 16 PRT Mus musculus188 Glu Gln Thr Gln Gln Ile Arg Leu Gln Ala Glu Ile Phe Gln Ala Arg 1 510 15 189 21 PRT Influenza virus 189 Glu Gln Thr Ser Leu Tyr Val Gln AlaSer Gly Arg Val Thr Val Ser 1 5 10 15 Thr Arg Arg Ser Gln 20 190 9 PRTHomo sapiens 190 Glu Ala Pro Gly Asn Tyr Pro Ala Leu 1 5 191 10 PRTPlasmodium falciparum 191 Glu Gln Tyr Leu Lys Lys Ile Lys Asn Ser 1 5 10192 15 PRT Homo sapiens 192 Glu Arg Ala Asp Leu Ile Ala Tyr Leu Lys GlnAla Thr Ala Lys 1 5 10 15 193 9 PRT Homo sapiens 193 Glu Arg Ala Lys IleArg Gly Ser Leu 1 5 194 20 PRT Homo sapiens 194 Glu Arg Glu Glu Ala LeuThr Thr Asn Val Trp Ile Glu Met Gln Trp 1 5 10 15 Cys Asp Tyr Arg 20 1959 PRT Influenza virus 195 Glu Arg Glu Leu Val Arg Lys Thr Arg 1 5 196 16PRT Human immunodeficiency virus 196 Glu Arg Phe Ala Val Asn Pro Gly LeuLeu Glu Thr Ser Glu Gly Cys 1 5 10 15 197 8 PRT Homo sapiens Xaa = anyamino acid 197 Glu Arg Phe Thr Xaa Ile Xaa Gly 1 5 198 16 PRT Homosapiens 198 Glu Arg Gly Pro Pro Gly Pro Gln Gly Ala Arg Gly Phe Pro GlyThr 1 5 10 15 199 25 PRT Mus musculus 199 Glu Arg Ile Thr Gln Ile AlaLys Gly Gln Glu Gln Trp Phe Arg Val 1 5 10 15 Asn Leu Arg Thr Leu LeuGly Tyr Tyr 20 25 200 9 PRT Homo sapiens 200 Glu Arg Leu Ala Ile Arg GlySer Leu 1 5 201 15 PRT Homo sapiens 201 Glu Ala Pro Val Val His Phe PheLys Asn Ile Val Thr Pro Arg 1 5 10 15 202 14 PRT Mycobacterium leprae202 Glu Arg Leu Ala Lys Leu Ala Gly Gly Val Ala Val Ile Lys 1 5 10 20328 PRT Mycobacterium leprae 203 Glu Arg Leu Ala Lys Leu Ala Gly Gly ValAla Val Ile Lys Ala Gly 1 5 10 15 Ala Ala Thr Glu Val Glu Leu Lys GluArg Lys His 20 25 204 9 PRT Homo sapiens 204 Glu Arg Leu Lys Ala Arg GlySer Leu 1 5 205 9 PRT Homo sapiens 205 Glu Arg Leu Lys Ile Ala Gly SerLeu 1 5 206 9 PRT Homo sapiens 206 Glu Arg Leu Lys Ile Arg Ala Ser Leu 15 207 9 PRT Homo sapiens 207 Glu Arg Leu Lys Ile Arg Gly Ala Leu 1 5 2089 PRT Homo sapiens 208 Glu Arg Leu Lys Ile Arg Gly Ser Ala 1 5 209 9 PRTHomo sapiens 209 Glu Arg Leu Lys Ile Arg Gly Ser Leu 1 5 210 16 PRTDrosophila 210 Glu Arg Leu Asn Ser Gln Asp Gln Gln Glu Asp Ser Ser LeuVal Glu 1 5 10 15 211 18 PRT Homo sapiens 211 Glu Arg Pro Thr Tyr ThrAsn Leu Asn Arg Leu Ile Gly Gln Ile Val 1 5 10 15 Ser Ser 212 11 PRTHomo sapiens 212 Glu Ala Val His Ala Ala His Ala Glu Ile Asn 1 5 10 2139 PRT Homo sapiens 213 Glu Arg Thr Leu His Leu Val Glu Leu 1 5 214 9 PRTHuman immunodeficiency virus 214 Glu Arg Tyr Leu Lys Asp Gln Gln Leu 1 5215 9 PRT Homo sapiens 215 Glu Arg Tyr Leu Lys Asp Gln Gln Leu 1 5 21610 PRT Homo sapiens 216 Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu 1 5 10217 10 PRT Human immunodeficiency virus 217 Glu Arg Tyr Leu Lys Asp GlnGln Leu Leu 1 5 10 218 11 PRT Human immunodeficiency virus 218 Glu ArgTyr Leu Lys Asp Gln Gln Leu Leu Gly 1 5 10 219 11 PRT Homo sapiens 219Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly 1 5 10 220 13 PRT Humanimmunodeficiency virus 220 Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu GlyIle Trp 1 5 10 221 13 PRT Homo sapiens 221 Glu Arg Tyr Leu Lys Asp GlnGln Leu Leu Gly Ile Trp 1 5 10 222 22 PRT Human immunodeficiency virus222 Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser 1 510 15 Gly Lys Leu Ile Cys Gly 20 223 10 PRT Homo sapiens 223 Glu Ala AlaGly Thr Gly Ile Leu Thr Val 1 5 10 224 8 PRT Homo sapiens 224 Glu AlaTyr Leu Gly Lys Lys Val 1 5 225 11 PRT Homo sapiens 225 Glu Arg Tyr LeuArg Asp Gln Gln Leu Leu Gly 1 5 10 226 9 PRT Homo sapiens 226 Glu ArgTyr Pro Arg Tyr Asn Gln Leu 1 5 227 9 PRT Homo sapiens 227 Glu Arg TyrGln Lys Ser Thr Glu Leu 1 5 228 11 PRT Homo sapiens Xaa = any amino acid228 Glu Ser Phe Leu Xaa Tyr Lys Lys Gly Ile Tyr 1 5 10 229 15 PRT Humanimmunodeficiency virus 229 Glu Ser Phe Arg Ser Gly Val Glu Thr Thr ThrPro Pro Gln Lys 1 5 10 15 230 9 PRT Homo sapiens 230 Glu Ser Gly Pro SerIle Val His Arg 1 5 231 10 PRT Homo sapiens 231 Glu Ser Gly Pro Ser IleVal His Arg Lys 1 5 10 232 10 PRT Homo sapiens 232 Glu Ser Leu Phe ArgAla Val Ile Thr Lys 1 5 10 233 11 PRT Gallus gallus 233 Glu Ser Asn PheAsn Thr Gln Ala Thr Asn Arg 1 5 10 234 12 PRT Influenza A virus 234 GluSer Thr Gly Asn Leu Ile Ala Pro Glu Tyr Gly 1 5 10 235 18 PRT Homosapiens Xaa = any amino acid 235 Glu Asp Glu Asn Leu Tyr Glu Gly Leu AsnLeu Asp Asp Xaa Ser Met 1 5 10 15 Tyr Glu 236 6 PRT Humanimmunodeficiency virus 236 Glu Ser Val Gln Ile Asn 1 5 237 20 PRT Homosapiens 237 Glu Ser Trp Gly Ala Val Trp Arg Ile Asp Thr Pro Asp Lys LeuThr 1 5 10 15 Gly Pro Phe Thr 20 238 11 PRT Homo sapiens 238 Glu Thr AspIle Ile Ile Asp Arg Ser Glu Tyr 1 5 10 239 11 PRT Homo sapiens 239 GluThr Asp Ile Ile Leu Asp Arg Ser Glu Tyr 1 5 10 240 11 PRT Homo sapiens240 Glu Thr Asp Ile Leu Ile Asp Arg Ser Glu Tyr 1 5 10 241 11 PRT Homosapiens 241 Glu Thr Asp Ile Leu Leu Asp Arg Ser Glu Tyr 1 5 10 242 11PRT Homo sapiens 242 Glu Thr Asp Leu Ile Ile Asp Arg Ser Glu Tyr 1 5 10243 11 PRT Homo sapiens 243 Glu Thr Asp Leu Ile Leu Asp Arg Ser Glu Tyr1 5 10 244 11 PRT Homo sapiens 244 Glu Thr Asp Leu Leu Ile Asp Arg SerGlu Tyr 1 5 10 245 11 PRT Homo sapiens 245 Glu Thr Asp Leu Leu Leu AspArg Ser Glu Tyr 1 5 10 246 17 PRT Plasmodium malariae 246 Glu Asp LysIle Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 247 11PRT Homo sapiens Xaa = any amino acid 247 Glu Thr Asp Xaa Xaa Xaa AspArg Ser Glu Tyr 1 5 10 248 10 PRT Homo sapiens 248 Glu Thr Phe Asn ThrPro Ala His Tyr Val 1 5 10 249 11 PRT Human immunodeficiency virus 249Glu Thr Phe Tyr Val Asp Gly Ala Ala Asn Arg 1 5 10 250 9 PRT Homosapiens 250 Glu Thr Ile Ile Pro Asp Trp Ser Tyr 1 5 251 9 PRT Homosapiens 251 Glu Thr Ile Leu Pro Asp Trp Ser Tyr 1 5 252 10 PRT Humanimmunodeficiency virus 252 Glu Thr Ile Asn Glu Glu Ala Ala Glu Trp 1 510 253 13 PRT Streptococcus sp 253 Glu Thr Leu Ala Lys Gln Ala Glu GluLeu Ala Lys Leu 1 5 10 254 9 PRT Homo sapiens 254 Glu Thr Leu Ile ProAsp Trp Ser Tyr 1 5 255 9 PRT Homo sapiens 255 Glu Thr Leu Leu Pro AspTrp Ser Tyr 1 5 256 12 PRT Homo sapiens 256 Glu Thr Leu Leu Arg Ala ValGlu Ser Tyr Leu Leu 1 5 10 257 9 PRT Influenza virus 257 Glu Asp Leu ArgVal Leu Ser Phe Ile 1 5 258 14 PRT Homo sapiens 258 Glu Thr Leu Leu ArgAla Val Glu Ser Tyr Leu Leu Ala His 1 5 10 259 16 PRT Homo sapiens 259Glu Thr Leu Leu Arg Ala Val Glu Ser Tyr Leu Leu Ala His Ser Asp 1 5 1015 260 8 PRT Human papillomavirus 260 Glu Thr Thr Asp Leu Tyr Cys Tyr 15 261 13 PRT Homo sapiens 261 Glu Thr Thr Glu Glu Ser Leu Arg Asn TyrTyr Glu Gly 1 5 10 262 13 PRT Homo sapiens 262 Glu Thr Thr Glu Glu SerLeu Arg Asn Tyr Tyr Glu Gln 1 5 10 263 11 PRT Homo sapiens 263 Glu ThrVal Ala Val Gly Val Ile Lys Ala Val 1 5 10 264 9 PRT Homo sapiens Xaa =any amino acid 264 Glu Thr Xaa Xaa Pro Asp Trp Ser Tyr 1 5 265 16 PRTHomo sapiens 265 Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln GluPro Glu 1 5 10 15 266 11 PRT Human immunodeficiency virus 266 Glu ThrTyr Tyr Val Asn Gly Ala Ala Asn Arg 1 5 10 267 20 PRT Homo sapiens 267Glu Val Ala Leu Cys Leu Pro Arg Ser Glu Leu Leu Phe Gln Gln Trp 1 5 1015 Gln Arg Gln Gly 20 268 11 PRT Plasmodium yoelii 268 Glu Asp Ser TyrVal Pro Ser Ala Glu Gln Ile 1 5 10 269 9 PRT Homo sapiens 269 Glu ValAla Pro Pro Glu Tyr His Arg 1 5 270 10 PRT Homo sapiens 270 Glu Val AlaPro Pro Glu Tyr His Arg Lys 1 5 10 271 9 PRT Homo sapiens 271 Glu ValAla Pro Pro Leu Leu Phe Val 1 5 272 13 PRT Schistosoma mansoni 272 GluVal Cys Val Arg Gln Leu Lys Ala Ile Ala Asn Lys 1 5 10 273 9 PRT Homosapiens 273 Glu Val Asp Pro Ile Gly His Leu Tyr 1 5 274 9 PRT Homosapiens 274 Glu Val Asp Pro Ile Gly His Ser Tyr 1 5 275 9 PRT Influenzavirus 275 Glu Val Asp Pro Ile Gly His Val Tyr 1 5 276 9 PRT Homo sapiens276 Glu Val Asp Pro Thr Ser Asn Thr Tyr 1 5 277 10 PRT Homo sapiens 277Glu Val Ile Leu Ile Asp Pro Phe His Lys 1 5 10 278 9 PRT Humanimmunodeficiency virus 278 Glu Val Ile Pro Met Phe Ser Ala Leu 1 5 27917 PRT Homo sapiens 279 Glu Asp Val Ile Pro Glu Gly Trp Lys Ala Asp ThrSer Tyr Ser Ala 1 5 10 15 Lys 280 17 PRT Plasmodium malariae 280 Glu ValLys Ile Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val281 11 PRT Human immunodeficiency virus 281 Glu Val Leu Val Trp Arg PheAsp Ser Lys Leu 1 5 10 282 15 PRT Human immunodeficiency virus 282 GluVal Val Ile Arg Ser Ala Asn Phe Thr Asp Asn Ala Lys Thr 1 5 10 15 283 9PRT Homo sapiens 283 Glu Val Val Pro Ile Ser His Leu Tyr 1 5 284 11 PRTHomo sapiens 284 Glu Val Trp Arg Glu Glu Ala Tyr His Ala Ala 1 5 10 28515 PRT Homo sapiens 285 Glu Val Trp Arg Glu Glu Ala Tyr His Ala Ala AspIle Lys Asp 1 5 10 15 286 11 PRT Rubella virus 286 Glu Val Trp Val ThrPro Val Ile Gly Ser Ala 1 5 10 287 18 PRT Rubella virus 287 Glu Val TrpVal Thr Pro Val Ile Gly Ser Ala Arg Lys Cys Gly Leu 1 5 10 15 His Ile288 12 PRT Rubella virus 288 Glu Val Trp Val Thr Pro Val Ile Gly Ser GlnAla 1 5 10 289 12 PRT Rubella virus 289 Glu Val Trp Val Thr Pro Val IleGly Thr Gln Ala 1 5 10 290 16 PRT Homo sapiens 290 Glu Glu Asp Phe HisVal Asp Gln Ala Thr Thr Val Lys Val Pro Met 1 5 10 15 291 10 PRT Humanpapillomavirus 291 Glu Val Tyr Asp Phe Ala Phe Arg Asp Leu 1 5 10 292 25PRT Human immunodeficiency virus 292 Glu Trp Arg Phe Asp Ser Arg Leu AlaPhe His His Val Ala Arg Glu 1 5 10 15 His Pro Glu Tyr Phe Asn Lys AsnLys 20 25 293 17 PRT Human immunodeficiency virus 293 Glu Trp Arg PheAsp Ser Arg Leu Ala Phe His His Val Ala Arg Glu 1 5 10 15 Leu 294 9 PRTHomo sapiens 294 Glu Trp Thr Ser Ser Asn Val Met Glu 1 5 295 10 PRT Homosapiens 295 Glu Trp Thr Ser Ser Asn Val Met Glu Glu 1 5 10 296 9 PRTHomo sapiens 296 Glu Trp Val Ser Leu Phe Arg Met Gln 1 5 297 9 PRT Homosapiens 297 Glu Trp Trp Gly Leu Gly Arg Trp Arg 1 5 298 9 PRTrespiratory syncytial virus 298 Glu Tyr Ala Leu Gly Val Val Gly Val 1 5299 17 PRT Homo sapiens 299 Glu Tyr Ile Leu Tyr Asn Lys Gly Ile Met GlyGlu Asp Ser Tyr Pro 1 5 10 15 Tyr 300 9 PRT Homo sapiens 300 Glu Tyr IleVal Leu Leu Phe Leu Leu 1 5 301 16 PRT Homo sapiens 301 Glu Glu Asp PheHis Val Asp Gln Val Thr Thr Val Lys Val Pro Met 1 5 10 15 302 18 PRTHomo sapiens 302 Glu Tyr Lys Leu Val Val Val Gly Ala Ala Gly Val Gly LysSer Ala 1 5 10 15 Leu Thr 303 18 PRT Homo sapiens 303 Glu Tyr Lys LeuVal Val Val Gly Ala Asp Gly Val Gly Lys Ser Ala 1 5 10 15 Leu Thr 304 18PRT Homo sapiens 304 Glu Tyr Lys Leu Val Val Val Gly Ala Gly Asp Val GlyLys Ser Ala 1 5 10 15 Leu Thr 305 18 PRT Homo sapiens 305 Glu Tyr LysLeu Val Val Val Gly Ala Arg Gly Val Gly Lys Ser Ala 1 5 10 15 Leu Thr306 18 PRT Homo sapiens 306 Glu Tyr Lys Leu Val Val Val Gly Ala Ser GlyVal Gly Lys Ser Ala 1 5 10 15 Leu Thr 307 10 PRT Mus musculus 307 GluTyr Lys Leu Val Val Val Gly Ala Val 1 5 10 308 18 PRT Homo sapiens 308Glu Tyr Lys Leu Val Val Val Gly Ala Val Gly Val Gly Lys Ser Ala 1 5 1015 Leu Thr 309 15 PRT Homo sapiens 309 Glu Tyr Leu Glu Asn Pro Lys LysTyr Ile Pro Gly Thr Lys Met 1 5 10 15 310 15 PRT Mus musculus 310 GluTyr Leu Ile Asn Val Ile His Ala Phe Gln Tyr Val Ile Gly 1 5 10 15 311 10PRT Plasmodium falciparum 311 Glu Tyr Leu Asn Lys Ile Gln Asn Ser Leu 15 10 312 8 PRT Homo sapiens 312 Glu Glu Asp Pro Val Lys Lys Val 1 5 3139 PRT Human papillomavirus 313 Glu Tyr Arg His Tyr Cys Tyr Ser Leu 1 5314 9 PRT Human T-cell lymphotropic virus 314 Glu Tyr Thr Asn Ile ProIle Ser Leu 1 5 315 9 PRT Homo sapiens 315 Glu Tyr Val Leu Leu Leu PheLeu Leu 1 5 316 9 PRT Homo sapiens 316 Glu Tyr Val Asn Ala Arg His CysLeu 1 5 317 16 PRT Homo sapiens 317 Glu Tyr Val Arg Phe Asp Ser Phe ValGly Glu Tyr Arg Ala Val Thr 1 5 10 15 318 14 PRT Homo sapiens 318 GluTyr Trp Asp Gly Glu Thr Arg Lys Val Lys Ala Gln Ser 1 5 10 319 14 PRTHomo sapiens 319 Glu Tyr Trp Asp Gly Glu Thr Arg Asn Met Lys Ala Ser Ala1 5 10 320 11 PRT Homo sapiens 320 Glu Tyr Trp Gln Ala Thr Trp Ile ProGlu Trp 1 5 10 321 20 PRT Homo sapiens 321 Gln Ala Ala Pro Ala Ile GlnAla Cys Val Glu Ala Cys Asn Leu Ile 1 5 10 15 Ala Cys Ala Arg 20 322 11PRT Homo sapiens 322 Gln Ala Asp His Ala Ala His Ala Glu Ile Asn 1 5 10323 20 PRT Human immunodeficiency virus 323 Glu Glu Glu Glu Val Gly PhePro Val Thr Pro Gln Val Pro Leu Arg 1 5 10 15 Pro Met Thr Tyr 20 324 9PRT Human papillomavirus type 16 324 Gln Ala Glu Pro Asp Arg Ala His Tyr1 5 325 10 PRT Hepatitis B virus 325 Gln Ala Phe Thr Phe Ser Pro Thr TyrLys 1 5 10 326 10 PRT Mus musculus 326 Gln Ala His Arg Ala Leu Asp LeuVal Ala 1 5 10 327 20 PRT Homo sapiens 327 Gln Ala His Ser Leu Glu ArgVal Cys His Cys Leu Gly Lys Trp Leu 1 5 10 15 Gly His Pro Asp 20 328 11PRT Homo sapiens 328 Gln Ala Ile His Ala Ala His Ala Glu Ile Asn 1 5 10329 14 PRT Homo sapiens 329 Gln Ala Ile Lys Ala Asn Ser Lys Phe Ile GlyIle Thr Glu 1 5 10 330 6 PRT Human immunodeficiency virus 330 Gln AlaIle Ser Pro Arg 1 5 331 11 PRT Human immunodeficiency virus 331 Gln AlaIle Ser Pro Arg Thr Leu Asn Ala Trp 1 5 10 332 19 PRT Homo sapiens 332Gln Ala Lys Phe Phe Ala Cys Ile Lys Arg Ser Asp Gly Ser Cys Ala 1 5 1015 Trp Tyr Arg 333 28 PRT Homo sapiens 333 Gln Ala Lys Phe Phe Ala CysIle Lys Arg Ser Asp Gly Ser Cys Ala 1 5 10 15 Trp Tyr Arg Gly Ala AlaPro Pro Lys Gln Glu Phe 20 25 334 9 PRT Homo sapiens 334 Glu Ala Asp AlaThr Gly His Ser Tyr 1 5 335 8 PRT Homo sapiens 335 Glu Glu Glu Pro ValLys Lys Ile 1 5 336 24 PRT Streptococcus sp 336 Gln Ala Lys Lys Ala ThrGlu Ala Glu Leu Asn Asn Leu Lys Ala Glu 1 5 10 15 Leu Ala Lys Val ThrGlu Gln Lys 20 337 9 PRT Epstein Barr virus 337 Gln Ala Lys Trp Arg LeuGln Thr Leu 1 5 338 11 PRT Homo sapiens 338 Gln Ala Leu His Ala Ala HisAla Glu Ile Asn 1 5 10 339 7 PRT Equus sp 339 Gln Ala Pro Gly Phe ThrTyr 1 5 340 9 PRT Homo sapiens 340 Gln Ala Pro Gly Asn Tyr Pro Ala Leu 15 341 11 PRT Homo sapiens 341 Gln Ala Arg His Ala Ala His Ala Glu IleAsn 1 5 10 342 14 PRT Homo sapiens 342 Gln Ala Arg Ile Leu Ala Val GluArg Tyr Leu Lys Asp Gln 1 5 10 343 9 PRT Human immunodeficiency virus343 Gln Ala Ser Gln Glu Val Lys Asn Trp 1 5 344 10 PRT Homo sapiens 344Gln Ala Ser Gln Glu Val Lys Asn Trp Met 1 5 10 345 13 PRT Homo sapiens345 Gln Ala Ser Gln Glu Val Lys Asn Trp Met Thr Glu Thr 1 5 10 346 11PRT Human immunodeficiency virus 346 Glu Glu Glu Val Gly Phe Pro Val ArgPro Gln 1 5 10 347 11 PRT Homo sapiens 347 Gln Ala Thr His Ala Ala HisAla Glu Ile Asn 1 5 10 348 28 PRT Homo sapiens 348 Gln Ala Thr Asn ArgAsn Thr Asp Gly Ser Thr Asp Tyr Gly Ile Leu 1 5 10 15 Gln Ile Asn SerArg Trp Trp Cys Asn Asp Gly Arg 20 25 349 11 PRT Homo sapiens 349 GlnAla Val Glu Ala Ala His Ala Glu Ile Asn 1 5 10 350 11 PRT Homo sapiens350 Gln Ala Val His Ala Ala Glu Ala Glu Ile Asn 1 5 10 351 11 PRT Homosapiens 351 Gln Ala Val His Ala Ala His Ala Asp Ile Asn 1 5 10 352 11PRT Homo sapiens 352 Gln Ala Val His Ala Ala His Ala Glu Asp Asn 1 5 10353 11 PRT Homo sapiens 353 Gln Ala Val His Ala Ala His Ala Glu Ile Asp1 5 10 354 11 PRT Homo sapiens 354 Gln Ala Val His Ala Ala His Ala GluIle Ile 1 5 10 355 11 PRT Homo sapiens 355 Gln Ala Val His Ala Ala HisAla Glu Ile Asn 1 5 10 356 15 PRT Homo sapiens 356 Gln Ala Val His AlaAla His Ala Glu Ile Asn Glu Ala Gly Arg 1 5 10 15 357 13 PRTMycobacterium leprae 357 Glu Glu Phe Ala Val Glu Phe Asp Leu Pro Gly IleLys 1 5 10 358 11 PRT Homo sapiens 358 Gln Ala Val His Ala Ala His AlaGlu Ile Gln 1 5 10 359 11 PRT Homo sapiens 359 Gln Ala Val His Ala AlaHis Ala Glu Ile Thr 1 5 10 360 11 PRT Homo sapiens 360 Gln Ala Val HisAla Ala His Ala Glu Ile Tyr 1 5 10 361 11 PRT Homo sapiens 361 Gln AlaVal His Ala Ala His Ala Glu Leu Asn 1 5 10 362 11 PRT Homo sapiens 362Gln Ala Val His Ala Ala His Ala Glu Arg Asn 1 5 10 363 11 PRT Homosapiens 363 Gln Ala Val His Ala Ala His Ala Glu Thr Asn 1 5 10 364 11PRT Homo sapiens 364 Gln Ala Val His Ala Ala His Ala Glu Tyr Asn 1 5 10365 11 PRT Homo sapiens 365 Gln Ala Val His Ala Ala His Ala Ile Ile Asn1 5 10 366 11 PRT Homo sapiens 366 Gln Ala Val His Ala Ala His Ala GlnIle Asn 1 5 10 367 11 PRT Homo sapiens 367 Gln Ala Val His Ala Ala HisAla Arg Ile Asn 1 5 10 368 9 PRT Homo sapiens 368 Glu Glu Phe Gln PheIle Lys Lys Ala 1 5 369 11 PRT Homo sapiens 369 Gln Ala Val His Ala AlaHis Ala Tyr Ile Asn 1 5 10 370 11 PRT Homo sapiens 370 Gln Ala Val HisAla Ala His Gly Glu Ile Asn 1 5 10 371 11 PRT Homo sapiens 371 Gln AlaVal His Ala Ala His Ser Glu Ile Asn 1 5 10 372 11 PRT Homo sapiens 372Gln Ala Val His Ala Ala His Val Glu Ile Asn 1 5 10 373 11 PRT Homosapiens 373 Gln Ala Val His Ala Ala Lys Ala Glu Ile Asn 1 5 10 374 11PRT Homo sapiens 374 Gln Ala Val His Ala Ala Leu Ala Glu Ile Asn 1 5 10375 11 PRT Homo sapiens 375 Gln Ala Val His Ala Ala Gln Ala Glu Ile Asn1 5 10 376 11 PRT Homo sapiens 376 Gln Ala Val His Ala Ala Arg Ala GluIle Asn 1 5 10 377 11 PRT Homo sapiens 377 Gln Ala Val His Ala Gly HisAla Glu Ile Asn 1 5 10 378 11 PRT Homo sapiens 378 Gln Ala Val His AlaArg His Ala Glu Ile Asn 1 5 10 379 13 PRT Mycobacterium leprae 379 GluGlu Phe Val Ala Glu Phe Asp Leu Pro Gly Ile Lys 1 5 10 380 11 PRT Homosapiens 380 Gln Ala Val His Ala Ser His Ala Glu Ile Asn 1 5 10 381 11PRT Homo sapiens 381 Gln Ala Val His Ala Val His Ala Glu Ile Asn 1 5 10382 11 PRT Homo sapiens 382 Gln Ala Val His Ala Tyr His Ala Glu Ile Asn1 5 10 383 11 PRT Homo sapiens 383 Gln Ala Val His Gly Ala His Ala GluIle Asn 1 5 10 384 11 PRT Homo sapiens 384 Gln Ala Val His Ser Ala HisAla Glu Ile Asn 1 5 10 385 11 PRT Homo sapiens 385 Gln Ala Val His ValAla His Ala Glu Ile Asn 1 5 10 386 11 PRT Homo sapiens 386 Gln Ala ValHis Tyr Ala His Ala Glu Ile Asn 1 5 10 387 11 PRT Homo sapiens 387 GlnAla Val Lys Ala Ala His Ala Glu Ile Asn 1 5 10 388 11 PRT Homo sapiens388 Gln Ala Val Leu Ala Ala His Ala Glu Ile Asn 1 5 10 389 11 PRT Homosapiens 389 Gln Ala Val Gln Ala Ala His Ala Glu Ile Asn 1 5 10 390 13PRT Mycobacterium leprae 390 Glu Glu Phe Val Val Ala Phe Asp Leu Pro GlyIle Lys 1 5 10 391 11 PRT Homo sapiens 391 Gln Ala Val Arg Ala Ala HisAla Glu Ile Asn 1 5 10 392 16 PRT Homo sapiens 392 Gln Asp Phe Leu ThrLys His Ala Ser His Thr Gly Ser Trp Ile Gly 1 5 10 15 393 15 PRT Homosapiens 393 Gln Asp Ile Leu Ile Arg Leu Phe Lys Ser His Pro Glu Thr Leu1 5 10 15 394 13 PRT Homo sapiens 394 Gln Asp Leu Glu Leu Ser Trp AsnLeu Asn Gly Leu Gln 1 5 10 395 14 PRT Homo sapiens 395 Gln Asp Leu GluLeu Ser Trp Asn Leu Asn Gly Leu Gln Ala 1 5 10 396 16 PRT Homo sapiens396 Gln Asp Leu Glu Leu Ser Trp Asn Leu Asn Gly Leu Gln Ala Asp Leu 1 510 15 397 15 PRT Homo sapiens 397 Gln Asp Val Asp Tyr Phe Arg His ProPro Glu Val Ser Leu Leu 1 5 10 15 398 15 PRT Mus musculus 398 Gln AspTyr Glu Tyr Leu Ile Asn Val Ile His Ala Phe Gln Tyr 1 5 10 15 399 9 PRTHomo sapiens 399 Gln Glu Glu Glu Gly Pro Ser Thr Phe 1 5 400 14 PRTClostridium tetani 400 Gln Glu Ile Lys Ala Asn Ser Lys Phe Ile Gly IleThr Glu 1 5 10 401 13 PRT Mycobacterium leprae 401 Glu Glu Phe Val ValGlu Ala Asp Leu Pro Gly Ile Lys 1 5 10 402 12 PRT Clostridium tetani 402Gln Glu Ile Tyr Met Gln His Thr Tyr Pro Ile Ser 1 5 10 403 17 PRT Homosapiens 403 Gln Glu Leu Lys Asn Lys Tyr Tyr Gln Val Pro Arg Lys Gly IleGln 1 5 10 15 Ala 404 8 PRT Influenza virus 404 Gln Glu Ser Thr Gly AsnLeu Ile 1 5 405 13 PRT Streptococcus sp 405 Gln Phe Gly Lys Glu Val HisAla Ala Asp Leu Leu Arg 1 5 10 406 10 PRT Homo sapiens 406 Gln Phe GlyAsn Asn Lys Thr Ile Val Phe 1 5 10 407 13 PRT Streptococcus sp 407 GlnPhe Gly Arg Glu Val His Ala Ala Asp Leu Leu Arg 1 5 10 408 14 PRTClostridium tetani 408 Gln Phe Ile Lys Ala Asn Ser Lys Phe Ile Gly IleThr Glu 1 5 10 409 19 PRT Homo sapiens 409 Gln Phe Leu Gly Gln Gln GlnPro Phe Pro Pro Gln Gln Pro Tyr Pro 1 5 10 15 Gln Pro Gln 410 10 PRTHuman papillomavirus 410 Gln Phe Leu Arg His Gln Asn Ile Glu Phe 1 5 10411 11 PRT Homo sapiens Xaa = any amino acid 411 Gln Phe Gln Pro Phe XaaTyr Phe Thr Asn Thr 1 5 10 412 13 PRT Mycobacterium leprae 412 Glu GluPhe Val Val Glu Phe Ala Leu Pro Gly Ile Lys 1 5 10 413 14 PRT Homosapiens 413 Gln Phe Val Ile Ala Asn Ala Ser Ser Val Ala Lys Thr Asp 1 510 414 17 PRT Homo sapiens 414 Gln Gly Ala Leu Ala Asn Ile Ala Val AspLys Ala Asn Leu Glu Ile 1 5 10 15 Met 415 13 PRT Homo sapiens 415 GlnGly Ala Arg Gly Gln Pro Gly Val Met Gly Phe Pro 1 5 10 416 15 PRT Humanimmunodeficiency virus 416 Gln Gly Ala Tyr Arg Ala Ile Arg His Ile ProArg Arg Ile Arg 1 5 10 15 417 15 PRT Simian adenovirus 417 Gln Gly PheAsn Asn Leu Asp Asn Leu Arg Asp Tyr Leu Asp Gly 1 5 10 15 418 13 PRTHomo sapiens 418 Gln Gly Phe Gln Gly Asn Pro Gly Glu Pro Gly Glu Pro 1 510 419 15 PRT Simian adenovirus 419 Gln Gly Ile Asn Asn Leu Asp Ile LeuArg Asp Tyr Leu Asp Gly 1 5 10 15 420 9 PRT Simian adenovirus 420 GlnGly Ile Asn Asn Leu Asp Asn Leu 1 5 421 15 PRT Simian adenovirus 421 GlnGly Ile Asn Asn Leu Asp Asn Leu Arg Asp Tyr Leu Asp Gly 1 5 10 15 422 24PRT Plasmodium yoelii 422 Gln Gly Pro Gly Ala Pro Gln Gly Pro Gly AlaPro Gln Gly Pro Gly 1 5 10 15 Ala Pro Gln Gly Pro Gly Ala Pro 20 423 13PRT Mycobacterium lactis 423 Glu Glu Phe Val Val Glu Phe Ala Leu Pro GlyIle Lys 1 5 10 424 11 PRT Homo sapiens 424 Gln Gly Val His Ala Ala HisAla Glu Ile Asn 1 5 10 425 9 PRT Homo sapiens 425 Gln Gly Trp Lys GlySer Pro Ala Ile 1 5 426 10 PRT Human immunodeficiency virus 426 Gln GlyTyr Phe Pro Asp Trp Gln Asn Tyr 1 5 10 427 11 PRT Clostridium tetani 427Gln Ile Gly Asn Asp Pro Asn Arg Asp Ile Leu 1 5 10 428 12 PRTMycobacterium leprae 428 Gln Ile Gln Val Tyr Gln Gly Glu Arg Glu Ile Ala1 5 10 429 9 PRT Homo sapiens 429 Gln Ile Arg Gly Arg Glu Arg Phe Glu 15 430 20 PRT Homo sapiens 430 Gln Ile Thr Gln Arg Lys Trp Glu Ala AlaArg Val Ala Glu Gln Asp 1 5 10 15 Arg Ala Tyr Leu 20 431 14 PRT Humanimmunodeficiency virus 431 Gln Ile Val Lys Lys Leu Arg Glu Gln Phe GlyAsn Asn Lys 1 5 10 432 26 PRT Homo sapiens 432 Gln Ile Tyr Pro Pro AsnAla Asn Lys Ile Arg Glu Ala Leu Ala Gln 1 5 10 15 Thr His Ser Ala IleAla His Tyr Trp Thr 20 25 433 10 PRT Human immunodeficiency virus 433Gln Ile Tyr Gln Glu Pro Phe Lys Asn Leu 1 5 10 434 13 PRT Mycobacteriumleprae 434 Glu Glu Phe Val Val Glu Phe Asp Ala Pro Gly Ile Lys 1 5 10435 11 PRT Human immunodeficiency virus 435 Gln Ile Tyr Gln Glu Pro PheLys Asn Leu Lys 1 5 10 436 13 PRT Human immunodeficiency virus 436 GlnIle Tyr Gln Glu Pro Phe Lys Asn Leu Lys Thr Gly 1 5 10 437 13 PRT Homosapiens 437 Gln Lys Phe Thr Gly Gly Ile Gly Asn Lys Leu Ala Ala 1 5 10438 10 PRT Homo sapiens 438 Gln Lys Phe Val Ala Cys Val Pro Gly Arg 1 510 439 20 PRT Human immunodeficiency virus 439 Gln Lys Gly Arg Gly SerArg Gly Gln His Gln Ala His Ser Leu Glu 1 5 10 15 Arg Val Cys His 20 44010 PRT Human immunodeficiency virus 440 Gln Lys Leu Val Gly Lys Leu AsnTrp Ala 1 5 10 441 15 PRT Human immunodeficiency virus 441 Gln Lys LeuTrp Gly Lys Leu Asn Trp Ala Ser Gln Ile Tyr Pro 1 5 10 15 442 16 PRTHuman immunodeficiency virus 442 Gln Lys Gln Glu Pro Ile Asp Lys Glu LeuTyr Pro Leu Thr Ser Leu 1 5 10 15 443 15 PRT Homo sapiens 443 Gln LysArg Ala Ala Val Asp Thr Tyr Cys Arg His Asn Tyr Gly 1 5 10 15 444 15 PRTHomo sapiens 444 Gln Lys Arg Ala Ala Tyr Asp Gln Tyr Gly His Ala Ala PheGlu 1 5 10 15 445 9 PRT Homo sapiens 445 Glu Ala Asp Pro Ala Gly His SerTyr 1 5 446 13 PRT Mycobacterium leprae 446 Glu Glu Phe Val Val Glu PheAsp Leu Ala Gly Ile Lys 1 5 10 447 16 PRT Homo sapiens 447 Gln Lys ArgAla Ala Tyr Asp Gln Tyr Gly His Ala Ala Phe Glu Cys 1 5 10 15 448 12 PRTStreptococcus sp 448 Gln Leu Ala Lys Gln Ala Glu Glu Leu Ala Lys Leu 1 510 449 9 PRT Homo sapiens 449 Gln Leu Ala Lys Thr Cys Pro Val Gln 1 5450 10 PRT Homo sapiens 450 Gln Leu Ala Lys Thr Cys Pro Val Gln Leu 1 510 451 10 PRT Human immunodeficiency virus 451 Gln Leu Cys Lys Leu LeuArg Gly Thr Lys 1 5 10 452 10 PRT Human immunodeficiency virus 452 GlnLeu Asp Cys Thr His Leu Glu Gly Lys 1 5 10 453 9 PRT Hepatitis B virus453 Gln Leu Phe His Leu Cys Leu Ile Ile 1 5 454 9 PRT Hepatitis C virus454 Gln Leu Phe Thr Phe Ser Pro Arg Arg 1 5 455 10 PRT Humanimmunodeficiency virus 455 Gln Leu Gly Ile Pro His Pro Ala Gly Leu 1 510 456 11 PRT Homo sapiens 456 Gln Leu Ile Ala Tyr Leu Lys Gln Ala ThrLys 1 5 10 457 13 PRT Mycobacterium leprae 457 Glu Glu Phe Val Val GluPhe Asp Leu Pro Ala Ile Lys 1 5 10 458 10 PRT Human immunodeficiencyvirus 458 Gln Leu Ile Lys Lys Glu Lys Val Tyr Leu 1 5 10 459 15 PRTHuman immunodeficiency virus 459 Gln Leu Leu Phe Ile His Phe Arg Ile GlyCys Arg His Ser Arg 1 5 10 15 460 10 PRT Hepatitis B virus 460 Gln LeuLeu Trp Phe His Ile Ser Cys Leu 1 5 10 461 13 PRT Sus scrofa 461 Gln LeuAsn Pro Glu Met Gly Thr Asp Asn Asp Ser Glu 1 5 10 462 9 PRT Humanimmunodeficiency virus 462 Gln Leu Gln Ala Arg Ile Leu Ala Val 1 5 46325 PRT Human immunodeficiency virus 463 Gln Leu Gln Ala Arg Ile Leu AlaVal Glu Arg Tyr Leu Lys Asp Gln 1 5 10 15 Gln Leu Leu Gly Ile Trp GlyCys Ser 20 25 464 10 PRT Hepatitis C virus 464 Gln Leu Arg Arg His IleAsp Leu Leu Val 1 5 10 465 20 PRT Epstein -Barr virus 465 Gln Leu SerAsp Thr Pro Leu Ile Pro Leu Thr Ile Phe Val Gly Glu 1 5 10 15 Asn ThrGly Val 20 466 9 PRT Homo sapiens 466 Gln Leu Ser Leu Leu Met Trp IleThr 1 5 467 9 PRT Mus musculus 467 Gln Leu Ser Pro Phe Pro Phe Asp Leu 15 468 13 PRT Mycobacterium leprae 468 Glu Glu Phe Val Val Glu Phe AspLeu Pro Gly Ala Lys 1 5 10 469 10 PRT Human immunodeficiency virus 469Gln Leu Thr Glu Ala Val Gln Lys Ile Thr 1 5 10 470 9 PRT Homo sapiens470 Gln Met Phe Cys Gln Leu Ala Lys Thr 1 5 471 9 PRT Homo sapiens 471Gln Met Leu Leu Ala Ile Ala Arg Leu 1 5 472 11 PRT Humanimmunodeficiency virus 472 Gln Met Val His Gln Ala Ile Ser Pro Arg Thr 15 10 473 10 PRT Homo sapiens 473 Gln Met Val Arg Thr Ala Ala Glu Val Ala1 5 10 474 13 PRT Homo sapiens 474 Gln Met Val Arg Thr Ala Ala Glu ValAla Gly Gln Leu 1 5 10 475 9 PRT Influenza virus 475 Gln Met Val Thr ThrThr Asn Pro Leu 1 5 476 9 PRT Homo sapiens 476 Gln Met Val Thr Thr ThrAsn Pro Leu 1 5 477 10 PRT Influenza virus 477 Gln Met Val Thr Thr ThrAsn Pro Leu Ile 1 5 10 478 9 PRT Homo sapiens 478 Gln Met Trp Gln AlaArg Leu Thr Val 1 5 479 13 PRT Mycobacterium leprae 479 Glu Glu Phe ValVal Glu Phe Asp Leu Pro Gly Ile Ala 1 5 10 480 10 PRT Mus musculus 480Gln Asn Ala Arg Ala Leu Asp Leu Val Ala 1 5 10 481 15 PRT Homo sapiens481 Gln Asn Phe Leu Leu Ser Asn Ala Pro Leu Gly Pro Gln Phe Pro 1 5 1015 482 16 PRT Homo sapiens 482 Gln Asn Phe Thr Val Ile Phe Asp Thr GlySer Ser Asn Leu Trp Val 1 5 10 15 483 24 PRT Homo sapiens 483 Gln AsnPhe Thr Val Ile Phe Asp Thr Gly Ser Ser Asn Leu Trp Val 1 5 10 15 ProSer Val Tyr Cys Thr Ser Pro 20 484 10 PRT Mus musculus 484 Gln Asn HisAla Ala Leu Asp Leu Val Ala 1 5 10 485 10 PRT Mus musculus 485 Gln AsnHis Arg Ala Ala Asp Leu Val Ala 1 5 10 486 10 PRT Mus musculus 486 GlnAsn His Arg Ala Leu Asp Ala Val Ala 1 5 10 487 8 PRT Mus musculus 487Gln Asn His Arg Ala Leu Asp Leu 1 5 488 10 PRT Mus musculus 488 Gln AsnHis Arg Ala Leu Asp Leu Ala Ala 1 5 10 489 10 PRT Mus musculus 489 GlnAsn His Arg Ala Leu Asp Leu Val Ala 1 5 10 490 13 PRT Mycobacteriumleprae 490 Glu Glu Phe Val Val Glu Phe Asp Leu Pro Gly Ile Lys 1 5 10491 10 PRT Mus musculus 491 Gln Asn His Arg Ala Leu Asp Leu Val Ile 1 510 492 15 PRT Homo sapiens 492 Gln Asn Ile Phe Leu Ser Asn Ala Pro LeuGly Pro Gln Phe Pro 1 5 10 15 493 15 PRT Homo sapiens 493 Gln Asn IleIle Leu Ser Asn Ala Pro Leu Gly Pro Gln Phe Pro 1 5 10 15 494 15 PRTHomo sapiens 494 Gln Asn Ile Leu Phe Ser Asn Ala Pro Leu Gly Pro Gln PhePro 1 5 10 15 495 15 PRT Homo sapiens 495 Gln Asn Ile Leu Leu Ser AsnAla Pro Leu Gly Pro Gln Phe Pro 1 5 10 15 496 15 PRT Homo sapiens 496Gln Asn Ile Leu Leu Ser Asn Ala Pro Gln Gly Pro Gln Phe Pro 1 5 10 15497 15 PRT Homo sapiens 497 Gln Asn Ile Leu Leu Ser Asn Ala Pro Val GlyPro Gln Phe Pro 1 5 10 15 498 15 PRT Homo sapiens 498 Gln Asn Ile LeuLeu Ser Asn Ala Gln Leu Gly Pro Gln Phe Pro 1 5 10 15 499 15 PRT Homosapiens 499 Gln Asn Ile Leu Leu Ser Asn Ala Val Leu Gly Pro Gln Phe Pro1 5 10 15 500 15 PRT Homo sapiens 500 Gln Asn Ile Leu Leu Ser Asn ValPro Leu Gly Pro Gln Phe Pro 1 5 10 15 501 9 PRT Homo sapiens 501 Glu GluPhe Tyr Val Asp Leu Glu Arg 1 5 502 15 PRT Homo sapiens 502 Gln Asn IleLeu Gln Ser Asn Ala Pro Leu Gly Pro Gln Phe Pro 1 5 10 15 503 15 PRTHomo sapiens 503 Gln Asn Ile Leu Val Ser Asn Ala Pro Leu Gly Pro Gln PhePro 1 5 10 15 504 15 PRT Homo sapiens 504 Gln Asn Ile Gln Leu Ser AsnAla Pro Leu Gly Pro Gln Phe Pro 1 5 10 15 505 15 PRT Homo sapiens 505Gln Asn Ile Val Leu Ser Asn Ala Pro Leu Gly Pro Gln Phe Pro 1 5 10 15506 15 PRT Homo sapiens 506 Gln Asn Val Leu Leu Ser Asn Ala Pro Leu GlyPro Gln Phe Pro 1 5 10 15 507 12 PRT Homo sapiens 507 Gln Pro Asp LeuArg Tyr Leu Phe Leu Asn Gly Asn 1 5 10 508 9 PRT Human papillomavirus508 Gln Pro Phe Ile Leu Tyr Ala His Ile 1 5 509 9 PRT Homo sapiens 509Gln Pro Phe Pro Ser Gln Gln Pro Tyr 1 5 510 11 PRT Epstein barr virus510 Gln Pro Ile Ser His Glu Glu Gln Pro Arg Tyr 1 5 10 511 9 PRT Humanpapillomavirus 511 Gln Pro Lys Lys Val Lys Arg Arg Leu 1 5 512 9 PRTInfluenza virus 512 Glu Glu Gly Ala Ile Val Gly Glu Ile 1 5 513 11 PRTEpstein barr virus 513 Gln Pro Leu Gly Thr Gln Asp Gln Ser Leu Tyr 1 510 514 9 PRT Human papillomavirus 514 Gln Pro Leu Thr Asp Ala Lys ValAla 1 5 515 11 PRT Epstein barr virus 515 Gln Pro Leu Thr Ser Pro ThrThr Ser Gln Leu 1 5 10 516 17 PRT Sendai virus 516 Gln Pro Met Leu PheLys Thr Ser Ile Pro Lys Leu Cys Lys Ala Glu 1 5 10 15 Gly 517 8 PRT Homosapiens 517 Gln Pro Gln Asn Gly Gln Phe Ile 1 5 518 15 PRT Lymphocyticchoriomeningitis virus 518 Gln Pro Gln Asn Gly Gln Phe Ile His Phe TyrArg Glu Pro Thr 1 5 10 15 519 9 PRT Staphylococcus erythraeus 519 GlnPro Gln Arg Gly Arg Glu Asn Phe 1 5 520 9 PRT Epstein barr virus 520 GlnPro Arg Ala Pro Ile Arg Pro Ile 1 5 521 11 PRT Epstein barr virus 521Gln Pro Arg Ala Pro Ile Arg Pro Ile Pro Thr 1 5 10 522 9 PRT Plasmodiumfalciparum 522 Gln Pro Arg Pro Arg Gly Asp Asn Phe 1 5 523 9 PRT Mumpsvirus 523 Glu Glu Lys Leu Ile Val Val Leu Phe 1 5 524 15 PRT Humanimmunodeficiency virus 524 Gln Gln His Leu Leu Gln Leu Thr Val Trp GlyIle Lys Gln Leu 1 5 10 15 525 9 PRT Human papillomavirus type 16 525 GlnGln Leu Leu Arg Arg Glu Val Tyr 1 5 526 9 PRT Homo sapiens 526 Gln GlnLeu Tyr Trp Ser His Pro Arg 1 5 527 16 PRT Influenza virus 527 Gln GlnArg Ala Ser Ala Gly Gln Ile Ser Val Gln Pro Ala Phe Ser 1 5 10 15 528 14PRT Homo sapiens 528 Gln Gln Arg Ser Lys Ile Leu Asp Ser Ile Gly Arg PhePhe 1 5 10 529 20 PRT Influenza virus 529 Gln Gln Thr Ile Ile Pro AsnIle Gly Ser Arg Pro Trp Val Arg Gly 1 5 10 15 Leu Ser Ser Arg 20 530 15PRT Epstein barr virus 530 Gln Gln Thr Asn Gln Ala Gly Gly Glu Ala ProGln Pro Gly Asp 1 5 10 15 531 16 PRT Homo sapiens 531 Gln Arg Ala ArgTyr Gln Trp Val Arg Cys Asn Pro Asp Ser Asn Ser 1 5 10 15 532 9 PRT Musmusculus 532 Gln Arg Gly Pro Gly Arg Ala Phe Val 1 5 533 11 PRT Musmusculus 533 Gln Arg Gly Pro Gly Arg Ala Phe Val Thr Ile 1 5 10 534 13PRT Streptococcus sp 534 Glu Glu Leu Ala Lys Gln Ala Glu Glu Leu Ala LysLeu 1 5 10 535 12 PRT Homo sapiens 535 Gln Arg Gly Pro Gly Arg Ala PheVal Thr Ile Gly 1 5 10 536 13 PRT Human immunodeficiency virus 536 GlnArg Gly Pro Gly Arg Ala Phe Val Thr Ile Gly Lys 1 5 10 537 9 PRT Homosapiens 537 Gln Arg His Gly Ser Lys Tyr Leu Ala 1 5 538 10 PRT Humanpapillomavirus 538 Gln Arg His Leu Asp Lys Lys Gln Arg Phe 1 5 10 539 16PRT Homo sapiens 539 Gln Arg Lys Thr Val Lys Cys Phe Asn Cys Gly Lys GluGly His Ile 1 5 10 15 540 9 PRT Chlamydia trachomatis 540 Gln Arg LeuGly Gly Gly Gly Gly Lys 1 5 541 9 PRT Escherichia coli 541 Gln Arg LeuLys Glu Ala Ala Glu Lys 1 5 542 9 PRT Homo sapiens 542 Gln Arg Pro GlyPhe Gly Tyr Gly Gly 1 5 543 11 PRT Homo sapiens 543 Gln Arg Val His AlaAla His Ala Glu Ile Asn 1 5 10 544 9 PRT Homo sapiens 544 Gln Arg TyrAsn Ala Met Arg Ala Ala 1 5 545 9 PRT Homo sapiens 545 Glu Glu Leu SerVal Leu Glu Val Phe 1 5 546 9 PRT Homo sapiens 546 Gln Arg Tyr Gln LysSer Thr Glu Leu 1 5 547 16 PRT Homo sapiens 547 Gln Ser Glu Ala Gly SerHis Thr Ile Gln Arg Met Tyr Gly Cys Asp 1 5 10 15 548 16 PRT Homosapiens 548 Gln Ser Glu Ala Gly Ser His Thr Val Gln Arg Met Tyr Gly CysAsp 1 5 10 15 549 13 PRT Homo sapiens 549 Gln Ser Glu Asp Gly Ser HisThr Ile Gln Ile Met Tyr 1 5 10 550 14 PRT Clostridium tetani 550 Gln SerIle Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 551 9 PRT Homosapiens 551 Gln Ser Thr Ser Arg His Lys Lys Leu 1 5 552 11 PRT Homosapiens 552 Gln Ser Val His Ala Ala His Ala Glu Ile Asn 1 5 10 553 25PRT Human immunodeficiency virus 553 Gln Thr Gly Ser Glu Glu Leu Arg SerLeu Tyr Asn Thr Val Ala Thr 1 5 10 15 Leu Tyr Cys Val His Gln Arg IleGlu 20 25 554 9 PRT Plasmodium falciparum 554 Gln Thr Asn Phe Lys SerLeu Leu Arg 1 5 555 24 PRT Rubella virus 555 Gln Thr Pro Ala Pro Lys ProSer Arg Ala Pro Pro Gln Gln Pro Gln 1 5 10 15 Pro Pro Arg Met Gln ThrGly Arg 20 556 10 PRT Homo sapiens 556 Glu Ala Asp Pro Pro Thr Gly HisSer Tyr 1 5 10 557 9 PRT Epstein Barr virus 557 Glu Glu Asn Leu Leu AspPhe Val Arg 1 5 558 15 PRT Mus musculus 558 Gln Thr Gln Gln Ile Arg LeuGln Ala Glu Ile Phe Gln Ala Arg 1 5 10 15 559 20 PRT Homo sapiens 559Gln Thr Thr Lys His Lys Trp Glu Ala Ala His Val Ala Glu Gln Trp 1 5 1015 Arg Ala Tyr Leu 20 560 9 PRT Homo sapiens 560 Gln Val Cys Glu Arg IlePro Thr Ile 1 5 561 9 PRT Homo sapiens 561 Gln Val Gly Lys Tyr Leu GlyLeu Gly 1 5 562 8 PRT Yersinia sp 562 Gln Val Gly Asn Thr Arg Thr Ile 15 563 11 PRT Hepatitis B virus 563 Gln Val Gly Val Gly Ala Phe Gly ProArg Leu 1 5 10 564 10 PRT Human immunodeficiency virus 564 Gln Val ProLeu Arg Pro His Thr Tyr Lys 1 5 10 565 10 PRT Human immunodeficiencyvirus 565 Gln Val Pro Leu Arg Pro Met Thr Phe Lys 1 5 10 566 10 PRTHuman immunodeficiency virus 566 Gln Val Pro Leu Arg Pro Met Thr Ser Lys1 5 10 567 10 PRT Human immunodeficiency virus 567 Gln Val Pro Leu ArgPro Met Thr Tyr Lys 1 5 10 568 10 PRT Epstein barr virus 568 Glu Glu AsnLeu Leu Asp Phe Val Arg Phe 1 5 10 569 10 PRT Human immunodeficiencyvirus 569 Gln Val Arg Asp Gln Ala Glu His Leu Lys 1 5 10 570 13 PRT Homosapiens 570 Gln Val Val Ala Leu Lys Pro Ala Ile Ala Ala Ala Ala 1 5 10571 11 PRT Homo sapiens 571 Gln Val Val His Ala Ala His Ala Glu Ile Asn1 5 10 572 15 PRT Human immunodeficiency virus 572 Gln Trp Gln Asn TyrThr Pro Gly Pro Gly Val Arg Tyr Pro Leu 1 5 10 15 573 14 PRT Homosapiens 573 Gln Tyr Ala Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 510 574 9 PRT Homo sapiens 574 Gln Tyr Asp Ala Ala Val Tyr Lys Leu 1 5575 9 PRT Homo sapiens 575 Gln Tyr Asp Asp Ala Gly Tyr Lys Leu 1 5 576 9PRT Homo sapiens 576 Gln Tyr Asp Asp Ala Val Ala Lys Leu 1 5 577 9 PRTHomo sapiens 577 Gln Tyr Asp Asp Ala Val Glu Lys Leu 1 5 578 9 PRT Homosapiens 578 Gln Tyr Asp Asp Ala Val Tyr Asp Leu 1 5 579 20 PRT EpsteinBarr virus 579 Glu Glu Asn Leu Leu Asp Phe Val Arg Phe Met Gly Val MetSer Ser 1 5 10 15 Cys Asn Asn Pro 20 580 9 PRT Homo sapiens 580 Gln TyrAsp Asp Ala Val Tyr Glu Leu 1 5 581 9 PRT Homo sapiens 581 Gln Tyr AspAsp Ala Val Tyr Phe Leu 1 5 582 9 PRT Homo sapiens 582 Gln Tyr Asp AspAla Val Tyr His Leu 1 5 583 9 PRT Homo sapiens 583 Gln Tyr Asp Asp AlaVal Tyr Lys Phe 1 5 584 9 PRT Homo sapiens 584 Gln Tyr Asp Asp Ala ValTyr Lys Leu 1 5 585 9 PRT Homo sapiens 585 Gln Tyr Asp Asp Ala Val TyrArg Leu 1 5 586 9 PRT Homo sapiens 586 Gln Tyr Asp Asp Ala Val Tyr SerLeu 1 5 587 9 PRT Homo sapiens 587 Gln Tyr Asp Asp Arg Val Tyr Lys Leu 15 588 9 PRT Homo sapiens 588 Gln Tyr Asp Glu Ala Val Ala Gln Phe 1 5 58911 PRT Plasmodium falciparum 589 Gln Tyr Asp Leu Phe Ile Tyr Asn Lys GlnLeu 1 5 10 590 16 PRT Homo sapiens 590 Glu Glu Asn Leu Arg Phe Asp SerAsp Val Gly Glu Phe Arg Ala Val 1 5 10 15 591 9 PRT Homo sapiens 591 GlnTyr Asp Gln Ile Pro Val Glu Ile 1 5 592 14 PRT Clostridium tetani 592Gln Tyr Ile Ala Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 593 14PRT Clostridium tetani 593 Gln Tyr Ile Ile Ala Asn Ser Lys Phe Ile GlyIle Thr Glu 1 5 10 594 14 PRT Clostridium tetani 594 Gln Tyr Ile Lys AlaAla Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 595 15 PRT Clostridium tetani595 Gln Tyr Ile Lys Ala Ala Ser Lys Phe Ile Gly Ile Thr Glu Leu 1 5 1015 596 14 PRT Clostridium tetani 596 Gln Tyr Ile Lys Ala Leu Ser Lys PheIle Gly Ile Thr Glu 1 5 10 597 14 PRT Clostridium tetani 597 Gln Tyr IleLys Ala Asn Ala Lys Phe Ile Gly Ile Thr Glu 1 5 10 598 14 PRTClostridium tetani 598 Gln Tyr Ile Lys Ala Asn Gln Lys Phe Ile Gly IleThr Glu 1 5 10 599 14 PRT Clostridium tetani 599 Gln Tyr Ile Lys Ala AsnSer Ala Phe Ile Gly Ile Thr Glu 1 5 10 600 14 PRT Clostridium tetani 600Gln Tyr Ile Lys Ala Asn Ser Glu Phe Ile Gly Ile Thr Glu 1 5 10 601 16PRT Homo sapiens 601 Glu Glu Asn Val Glu His Asp Ala Glu Glu Asn Val GluHis Asp Ala 1 5 10 15 602 13 PRT Clostridium tetani 602 Gln Tyr Ile LysAla Asn Ser Phe Ile Gly Ile Thr Glu 1 5 10 603 14 PRT Clostridium tetani603 Gln Tyr Ile Lys Ala Asn Ser Lys Ala Ile Gly Ile Thr Glu 1 5 10 60414 PRT Clostridium tetani 604 Gln Tyr Ile Lys Ala Asn Ser Lys Glu IleGly Ile Thr Glu 1 5 10 605 14 PRT Clostridium tetani 605 Gln Tyr Ile LysAla Asn Ser Lys Phe Ala Gly Ile Thr Glu 1 5 10 606 14 PRT Clostridiumtetani 606 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Ala Ile Thr Glu 1 510 607 14 PRT Clostridium tetani 607 Gln Tyr Ile Lys Ala Asn Ser Lys PheIle Gly Ala Thr Glu 1 5 10 608 12 PRT Clostridium tetani 608 Gln Tyr IleLys Ala Asn Ser Lys Phe Ile Gly Ile 1 5 10 609 14 PRT Clostridium tetani609 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Ala Glu 1 5 10 61014 PRT Clostridium tetani 610 Gln Tyr Ile Lys Ala Asn Ser Lys Phe IleGly Ile Phe Glu 1 5 10 611 14 PRT Clostridium tetani 611 Gln Tyr Ile LysAla Asn Ser Lys Phe Ile Gly Ile Lys Glu 1 5 10 612 11 PRT Mus musculus612 Glu Glu Gln Thr Gln Gln Ile Arg Leu Gln Ala 1 5 10 613 14 PRTClostridium tetani 613 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly IleSer Glu 1 5 10 614 13 PRT Clostridium tetani 614 Gln Tyr Ile Lys Ala AsnSer Lys Phe Ile Gly Ile Thr 1 5 10 615 14 PRT Clostridium tetani 615 GlnTyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Ala 1 5 10 616 14 PRTClostridium tetani 616 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly IleThr Asp 1 5 10 617 14 PRT Clostridium tetani 617 Gln Tyr Ile Lys Ala AsnSer Lys Phe Ile Gly Ile Thr Glu 1 5 10 618 15 PRT Clostridium tetani 618Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu Leu 1 5 10 15619 17 PRT Clostridium tetani 619 Gln Tyr Ile Lys Ala Asn Ser Lys PheIle Gly Ile Thr Glu Leu Lys 1 5 10 15 Lys 620 19 PRT Clostridium tetani620 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu Leu Lys 1 510 15 Lys Leu Glu 621 14 PRT Clostridium tetani 621 Gln Tyr Ile Lys AlaAsn Ser Lys Phe Ile Gly Ile Thr Lys 1 5 10 622 14 PRT Clostridium tetani622 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Lys 1 5 10 62313 PRT Mus musculus 623 Glu Glu Gln Thr Gln Gln Ile Arg Leu Gln Ala GluIle 1 5 10 624 14 PRT Clostridium tetani 624 Gln Tyr Ile Lys Ala Asn SerLys Phe Ile Gly Ile Thr Val 1 5 10 625 14 PRT Clostridium tetani 625 GlnTyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Lys Thr Glu 1 5 10 626 14 PRTClostridium tetani 626 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly LeuThr Glu 1 5 10 627 14 PRT Clostridium tetani 627 Gln Tyr Ile Lys Ala AsnSer Lys Phe Ile Gly Gln Thr Glu 1 5 10 628 14 PRT Clostridium tetani 628Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gln Ile Thr Glu 1 5 10 629 14PRT Clostridium tetani 629 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile GlnIle Thr Glu 1 5 10 630 14 PRT Clostridium tetani 630 Gln Tyr Ile Lys AlaAsn Ser Lys Phe Ile Tyr Ile Thr Glu 1 5 10 631 14 PRT Clostridium tetani631 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Lys Gly Ile Thr Glu 1 5 10 63214 PRT Clostridium tetani 632 Gln Tyr Ile Lys Ala Asn Ser Lys Phe GlnGly Ile Thr Glu 1 5 10 633 14 PRT Clostridium tetani 633 Gln Tyr Ile LysAla Asn Ser Lys Phe Val Gly Ile Thr Glu 1 5 10 634 14 PRT Mus musculus634 Glu Glu Gln Thr Gln Gln Ile Arg Leu Gln Ala Glu Ile Phe 1 5 10 63514 PRT Clostridium tetani 635 Gln Tyr Ile Lys Ala Asn Ser Lys Ser IleGly Ile Thr Glu 1 5 10 636 14 PRT Clostridium tetani 636 Gln Tyr Ile LysAla Asn Ser Lys Tyr Ile Gly Ile Thr Glu 1 5 10 637 14 PRT Clostridiumtetani 637 Gln Tyr Ile Lys Ala Asn Ser Arg Phe Ile Gly Ile Thr Glu 1 510 638 14 PRT Clostridium tetani 638 Gln Tyr Ile Lys Ala Asn Ser Ser PheIle Gly Ile Thr Glu 1 5 10 639 14 PRT Clostridium tetani 639 Gln Tyr IleLys Ala Asn Tyr Lys Phe Ile Gly Ile Thr Glu 1 5 10 640 14 PRTClostridium tetani 640 Gln Tyr Ile Lys Ala Gln Ser Lys Phe Ile Gly IleThr Glu 1 5 10 641 14 PRT Clostridium tetani 641 Gln Tyr Ile Lys Phe AsnSer Lys Phe Ile Gly Ile Thr Glu 1 5 10 642 14 PRT Clostridium tetani 642Gln Tyr Ile Lys Lys Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 643 14PRT Clostridium tetani 643 Gln Tyr Ile Lys Ser Asn Ser Lys Phe Ile GlyIle Thr Glu 1 5 10 644 14 PRT Clostridium tetani 644 Gln Tyr Ile Arg AlaAsn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 645 15 PRT Mus musculus 645Glu Glu Gln Thr Gln Gln Ile Arg Leu Gln Ala Glu Ile Phe Gln 1 5 10 15646 14 PRT Clostridium tetani 646 Gln Tyr Ile Ser Ala Asn Ser Lys PheIle Gly Ile Thr Glu 1 5 10 647 14 PRT Clostridium tetani 647 Gln Tyr LysLys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 648 9 PRT Homosapiens 648 Gln Tyr Leu Ala Gly Leu Ser Thr Leu 1 5 649 9 PRT Homosapiens 649 Gln Tyr Leu Ala Leu Ala Ala Leu Ile 1 5 650 9 PRT Plasmodiumfalciparum 650 Gln Tyr Leu Lys Lys Ile Lys Asn Ser 1 5 651 20 PRTPlasmodium falciparum 651 Gln Tyr Leu Lys Lys Ile Lys Asn Ser Ile SerThr Glu Trp Ser Pro 1 5 10 15 Cys Ser Val Thr 20 652 10 PRT Plasmodiumfalciparum 652 Gln Tyr Leu Lys Lys Ile Lys Asn Ser Leu 1 5 10 653 13 PRTHomo sapiens 653 Gln Tyr Met Arg Ala Asp Gln Ala Ala Gly Gly Leu Arg 1 510 654 10 PRT Human papillomavirus 654 Gln Tyr Asn Lys Pro Leu Cys AspAsp Leu 1 5 10 655 9 PRT Homo sapiens 655 Gln Tyr Asn Val Leu Pro GlnGly Trp 1 5 656 17 PRT Mus musculus 656 Glu Glu Gln Thr Gln Gln Ile ArgLeu Gln Ala Glu Ile Phe Gln Ala 1 5 10 15 Arg 657 14 PRT Clostridiumtetani 657 Gln Tyr Gln Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu 1 510 658 11 PRT Homo sapiens 658 Gln Tyr Arg Arg Ala Leu Asp Leu Val AlaAla 1 5 10 659 11 PRT Homo sapiens 659 Gln Tyr Val His Ala Ala His AlaGlu Ile Asn 1 5 10 660 14 PRT Clostridium tetani 660 Gln Tyr Val Lys AlaAsn Ser Lys Phe Ile Gly Ile Thr Glu 1 5 10 661 10 PRT Homo sapiens 661Gln Tyr Val Lys Gln Asn Thr Leu Lys Leu 1 5 10 662 9 PRT Homo sapiens662 Glu Ala Asp Pro Thr Ala His Ser Tyr 1 5 663 15 PRT Humanimmunodeficiency virus 663 Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn GluGln Glu Leu Leu 1 5 10 15 664 8 PRT Influenza virus 664 Glu Glu Ser ThrGly Asn Leu Ile 1 5 665 15 PRT Homo sapiens 665 Glu Glu Val Asp Met ThrPro Ala Asp Ala Leu Asp Asp Phe Asp 1 5 10 15 666 11 PRT Humanimmunodeficiency virus 666 Glu Glu Val Gly Phe Pro Val Arg Pro Gln Val 15 10 667 15 PRT Human immunodeficiency virus 667 Glu Phe Phe Tyr Cys AsnThr Thr Gln Leu Phe Asn Asn Thr Trp 1 5 10 15 668 11 PRT Homo sapiens668 Glu Phe Ile Ser Glu Ala Ile Ile His Val Leu 1 5 10 669 9 PRT Homosapiens 669 Glu Phe Gln Ala Ala Ile Ser Arg Lys 1 5 670 8 PRT Homosapiens 670 Glu Phe Val Asn Thr Pro Pro Leu 1 5 671 12 PRT Homo sapiens671 Glu Phe Trp Glu Phe Asp Leu Pro Gly Ile Lys Ala 1 5 10 672 8 PRTInfluenza virus 672 Glu Gly Ala Ile Val Gly Glu Ile 1 5 673 9 PRT Homosapiens 673 Glu Ala Asp Pro Thr Gly Ala Ser Tyr 1 5 674 15 PRT Homosapiens 674 Glu Gly Phe Ser Tyr Thr Asp Ala Asn Lys Asn Lys Gly Ile Val1 5 10 15 675 8 PRT Influenza A virus 675 Glu Gly Gly Trp Thr Gly MetIle 1 5 676 12 PRT Influenza virus 676 Glu Gly Ile Leu Gly Phe Val PheThr Leu Thr Val 1 5 10 677 17 PRT Plasmodium malariae 677 Glu Gly LysIle Ala Lys Met Glu Lys Ala Ser Ser Val Phe Asn Val 1 5 10 15 Val 678 13PRT Homo sapiens 678 Glu Gly Met Arg Phe Asp Lys Gly Tyr Ile Ser Gly Tyr1 5 10 679 20 PRT Homo sapiens 679 Glu Gly Gln Leu Val Ser Ile His SerPro Glu Glu Gln Asp Phe Leu 1 5 10 15 Thr Lys His Ala 20 680 9 PRT Homosapiens 680 Glu Gly Gln Arg Pro Gly Phe Gly Tyr 1 5 681 9 PRT Homosapiens 681 Glu His Ala Gly Val Ile Ser Val Leu 1 5 682 23 PRT Homosapiens 682 Glu His His Ile Phe Leu Gly Ala Thr Asn Tyr Ile Tyr Val LeuAsn 1 5 10 15 Glu Glu Asp Leu Gln Lys Val 20 683 17 PRT Homo sapiens 683Glu His Pro Ser Leu Gln Ser Pro Ile Thr Val Glu Trp Arg Leu Leu 1 5 1015 His 684 9 PRT Homo sapiens 684 Glu Ala Asp Pro Thr Gly His Ala Tyr 15 685 15 PRT Mycobacterium tuberculosis 685 Glu His Arg Val Lys Arg GlyLeu Thr Val Ala Val Ala Gly Ala 1 5 10 15 686 13 PRT Homo sapiens 686Glu Ile Ala Tyr Asp Ile Cys Arg Arg Asn Leu Asp Ile 1 5 10 687 17 PRTHomo sapiens 687 Glu Ile Ala Tyr Asp Ile Cys Arg Arg Asn Leu Asp Ile GluArg Pro 1 5 10 15 Thr 688 17 PRT Human immunodeficiency virus type 1 688Glu Ile Cys Thr Glu Met Glu Lys Glu Gly Lys Ile Ser Lys Ile Gly 1 5 1015 Pro 689 9 PRT Human papillomavirus type 16 689 Glu Ile Asp Gly ProAla Gly Gln Ala 1 5 690 16 PRT Human immunodeficiency virus 690 Glu IleAsp Asn Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Cys 1 5 10 15 691 10PRT Homo sapiens 691 Glu Ile Lys Ala Asn Ser Lys Phe Ile Gly 1 5 10 6929 PRT Human immunodeficiency virus 692 Glu Ile Lys Asp Thr Lys Glu AlaLeu 1 5 693 15 PRT Human immunodeficiency virus 693 Glu Ile Lys Asp ThrLys Glu Ala Leu Asp Lys Ile Glu Glu Glu 1 5 10 15 694 16 PRT Humanimmunodeficiency virus 694 Glu Ile Lys Ile Leu Asn Ile Phe Gly Val IleLys Gly Phe Val Glu 1 5 10 15 695 25 PRT Human immunodeficiency virusMUTAGEN (25) Xaa = Lys branched with a Palm-NH2 moiety 695 Glu Trp ArgPhe Asp Ser Arg Leu Ala Phe His His Val Ala Arg Glu 1 5 10 15 His ProGlu Tyr Phe Asn Lys Asn Xaa 20 25 696 10 PRT Homo sapiens MOD_RES (1)PYRROLIDONE CARBOXYLIC ACID 696 Xaa Leu Ala Gly Ile Gly Ile Leu Thr Val1 5 10 697 10 PRT Homo sapiens MUTAGEN (1) Xaa = glutamic acidacetylated on amine functional group 697 Xaa Leu Ala Gly Ile Gly Ile LeuThr Val 1 5 10

1. A molecule of pharmaceutical interest containing at its N-terminalend a glutamic acid or a glutamine, characterized in that it exists inthe form of a physiologically acceptable addition salt with a strongacid.
 2. The molecule of pharmaceutical interest as claimed in claim 1,characterized in that it is an MHC ligand containing at its N-terminalend a glutamic acid or a glutamine.
 3. The molecule of pharmaceuticalinterest as claimed in claim 1 or 2, characterized in that thephysiologically acceptable addition salt with a strong acid is chosenfrom the addition salts with inorganic or organic acids preferably fromthe methanesulfonate, hydrochloride, hydrobromide, sulfate, nitrate andphosphate.
 4. The molecule of pharmaceutical interest as claimed in oneof claims 1 to 3, characterized in that it is chosen from natural orsynthetic molecules.
 5. The molecule of pharmaceutical interest asclaimed in one of claims 1 to 4, characterized in that it is chosen fromthe group consisting of proteins, peptides, multi-epitope polypeptideconstructs, pseudopeptides, retro-inverso, peptoids, peptidomimetics andlipopeptides.
 6. The MHC ligand as claimed in one of claims 2 to 4,characterized in that it is chosen from the CTL epitopes.
 7. The MHCligand as claimed in claim 6, characterized in that it is chosen fromthe CTL Epitopes existing in the form of an octapeptide, nonapeptide ordecapeptide.
 8. The MHC ligand as claimed in one of claims 2 to 4,characterized in that it is chosen from the ligands described in thedatabases SYFPEITHI or MHCPEP containing a glutamic acid or a glutamineat their N-terminal end.
 9. The MHC ligand as claimed in either ofclaims 2 and 3, characterized in that it is chosen from the peptides SEQID No. 1 to SEQ ID No.
 695. 10. The MHC ligand as claimed in one ofclaims 2 to 7, characterized in that it is chosen from the group ofpeptides corresponding to SEQ ID No. 81, SEQ ID No. 112, SEQ ID No. 2,SEQ ID No. 273, SEQ ID No. 110, SEQ ID No. 106, SEQ ID No. 10, SEQ IDNo. 692, SEQ ID No. 257, SEQ ID No. 568, SEQ ID No. 464, SEQ ID No. 466,SEQ ID No. 567 and SEQ ID No.
 695. 11. The MHC ligand as claimed inclaim 10, characterized in that it is the peptide corresponding to SEQID No. 81, in hydrochloride or sulfate form.
 12. A pharmaceuticalcomposition, characterized in that it comprises at least one molecule ofpharmaceutical interest as claimed in one of claims 1 to
 11. 13. Avaccine, characterized in that it comprises at least one MHC ligand asclaimed in one of claims 2 to
 11. 14. The vaccine as claimed in claim13, characterized in that it comprises, in addition, at least oneadjuvant.
 15. The vaccine as claimed in claim 13 or 14, characterized inthat the adjuvant is chosen from the salts of Aluminum (Alum) or ofCalcium, the enterobacterial OmpA proteins, TT, DT, CRM197, PLGA, ISCOM,Montanide ISA 720, aliphatic quaternary ammoniums, MPL-A, Quil-A, CpGs,Leif, CT, LT or the detoxified versions of CT or LT.
 16. The vaccine asclaimed in one of claims 13 to 15, characterized in that it comprises,in addition, a carrier compound mixed with or coupled to said ligand.17. The vaccine as claimed in claim 15, characterized in that saidcarrier compound is chosen from toxoids, including the diphtheria toxoidor the tetanus toxoid, proteins derived from streptococcus, bacterialouter membrane proteins of the OmpA type, outer membrane proteincomplexes (OMPC), outer membrane vesicles (OMV) or HSPs.
 18. The vaccineas claimed in one of claims 13 to 17, characterized in that said ligandoptionally combined with a carrier compound is incorporated into avector chosen from the group comprising liposomes, virosomes,nanospheres, microspheres, microcapsules or biovectors.
 19. Ananti-melanoma vaccine, characterized in that it comprises at least onepeptide as claimed in claim
 11. 20. The anti-melanoma vaccine as claimedin claim 19, characterized in that it comprises, in addition, anenterobacterial OmpA protein.
 21. A method for the in vitro diagnosis ofpathologies associated with the presence, in a patient's body, of MHCligands, and which may be directly or indirectly involved in the processof development of these pathologies in humans or , animals,characterized in that it comprises the steps of: bringing a biologicalsample obtained from a patient, in particular blood or any biologicalsample which may contain lymphocytes, into contact with an MHC ligandaccording to the invention, under conditions allowing the formation of abinary complex between said MHC ligand and the MHC molecules present insaid sample, and the reaction between said binary complex and the T cellreceptors which may be present in said biological sample, detecting invitro the ternary complex MHC—MHC ligand—T receptor, which may be formedin the preceding step.
 22. A pack or kit for carrying out diagnosticmethods in vitro as claimed in claim 21, comprising: an MHC ligandaccording to one of claims 2 to 11; optionally reagents to allow theformation of an immunological reaction between said ligand, the MHCmolecules and the T cell receptors which may be present in thebiological sample; optionally reagents which make it possible to detectthe ternary complex according to the invention, which was produced atthe end of the immunological reaction, said reagents optionallycontaining a marker or being capable of being recognized in turn by alabeled reagent.
 23. The use of a ligand as claimed in one of claims 2to 10, for the preparation of a vaccine intended for the prophylactic ortherapeutic treatment of viral, bacterial, parasitic or fungalinfections.
 24. The use of a ligand as claimed in one of claims 2 to 11,for the preparation of a vaccine intended for the prophylactic ortherapeutic treatment of cancers, and preferably for inhibiting thegrowth of tumors.
 25. The use of a physiologically acceptable strongacid for stabilizing and maintaining the biological activity of amolecule with pharmaceutical activity containing a glutamic acid or aglutamine at its N-terminal end.
 26. The use of a strong acid forreducing and/or suppressing the formation of the pyroglutamic derivativeof a molecule with pharmaceutical activity containing a glutamic acid ora glutamine at its N-terminal end.
 27. A method for preparing a moleculeof pharmaceutical interest containing a glutamic acid or a glutamine atits N-terminal end in the form of a physiologically acceptable additionsalt with a strong acid as claimed in one of claims 1 to 11,characterized in that it comprises a step of purifying by RP-HPLC saidmolecule from the corresponding trifluoroacetate salt using an eluentbased on said strong acid, optionally followed by a step offreeze-drying the solution thus obtained.
 28. A method for preparing amolecule of pharmaceutical interest containing a glutamic acid or aglutamine at its N-terminal end in the form of a physiologicallyacceptable addition salt with a strong acid as claimed in one of claims1 to 11, characterized in that it comprises a step of dissolving atrifluoroacetate salt of said molecule in a solution of said strong acidin excess, optionally followed by a step of freeze-drying the solutionthus obtained.
 29. A method for preparing a molecule of pharmaceuticalinterest containing a glutamic acid or a glutamine at its N-terminal endin the form of a physiologically acceptable addition salt with a strongacid as claimed in one of claims 1 to 11, characterized in that itcomprises an ion-exchange chromatography step starting with thecorresponding trifluoroacetate salt of said molecule of pharmaceuticalinterest, after dissolving said salt in a solution containing saidstrong acid.
 30. A method for stabilizing a molecule of pharmaceuticalinterest containing a glutamic acid or a glutamine at its N-terminalend, characterized in that said molecule is reacted with a strong acidunder conditions which make it possible to obtain said molecule in theform of a physiologically acceptable addition salt with a strong acid,in particular according to a method as claimed in one of claims 27 to29.